Journal articles on the topic 'Antidepressants Mechanisms of action'
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Kozlovskii, V. L., M. Yu Popov, D. N. Kosterin, and O. V. Lepik. "Heterogeneity of the mechanisms of action of antidepressants." V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY, no. 1 (April 12, 2021): 11–17. http://dx.doi.org/10.31363/2313-7053-2021-1-11-17.
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The article discusses the heterogeneous mechanisms of the pharmacodynamics of antidepressants that underlie the therapeutic response. Sharing the similar clinical activity, antidepressants determine the development of drug-induced homeostasis by means of different molecular mechanisms (selective or nonselective blockade of monoamine reuptake, inhibition of monoamine oxidase, blockade of certain monoamine receptors). However, an increase of serotonin and other monoamines concentrations in the synapses of the central nervous system is only the initiating factor in the development of specific clinical effects. The latter are probably determined by other neurochemical effects, including changes in the density of postsynaptic receptors and an increase in the synthesis of neurotrophic factors. However, the primary mechanisms that increase monoamine concentrations in the synapses might not always “work properly”, leading to the lack of efficacy of the initial antidepressant, while the probability of the therapeutic response to the subsequent antidepressant remains rather high. Thus, the efficacy of an antidepressant may depend on the baseline differences in the neurochemical state contributing to the pathological “depressive” homeostasis. The heterogeneous neurochemical effects of antidepressants can determine the dissociation of existing neuronal interactions, leading to the development of the new — druginduced — homeostasis. At the same time, it is possible that stimulation of general neurotrophic processes by antidepressants may contribute to the progression and chronicity of pathology due to the ambiguous influence on certain stages of the pathological process. This determines the significance of neurophysiological studies of central disturbances in depression and search of fundamentally new neurochemical targets for the treatment of depressive states associated with various mental disorders.
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Amidfar, Meysam, and Yong-Ku Kim. "Recent Developments on Future Antidepressant-related Serotonin Receptors." Current Pharmaceutical Design 24, no. 22 (October 19, 2018): 2541–48. http://dx.doi.org/10.2174/1381612824666180803111240.
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Conventional serotonin-enhancing antidepressants including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) have shown effectiveness in the treatment of major depression, but their significant limitations such as slowness of action have led to intensive research efforts to develop new antidepressants. Increased synaptic neurotransmission of serotonin (5-hdroxytryptamine; 5-HT) through orchestration of stimulation and blockade of various subtypes of 5-HT receptors is involved in the mechanisms of action of SSRIs. Agonists at the 5-HT1A, 5-HT1B, 5-HT2C, 5-HT4, and 5-HT6 receptors and antagonists at the 5-HT1A, 5-HT2A, 5-HT2C, 5-HT3, 5- HT6, and 5-HT7 receptors have shown antidepressant properties in clinical and preclinical studies. However, paradoxical antidepressant-like effects of both agonists and antagonists at particular 5-HT receptors suggest the need to consider the neurochemical mechanisms of each 5-HT receptor subtype. Therefore, better knowledge of the involvement of individual 5-HT receptors in the mechanisms of action of currently used antidepressants as well as antidepressant effects of selective ligands of 5- HT receptor subtypes will provide opportunities for the development of future antidepressants with more rapid onset of action, fewer side effects, and better efficacy than SSRIs.
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Leonard, B. E. "Mechanisms of Action of Antidepressants." CNS Drugs 4, Supplement 1 (1995): 1–12. http://dx.doi.org/10.2165/00023210-199500041-00003.
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GARATTINI, S., C. BARBUI, and B. SARACENO. "Antidepressant agents: from tricyclics to serotonin uptake inhibitors." Psychological Medicine 28, no. 5 (September 1998): 1169–78. http://dx.doi.org/10.1017/s0033291798007090.
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Background. The number of antidepressant drugs available in the market has grown rapidly in the last few years. The present paper underlines some of the pre-clinical and clinical problems that call close attention from the regulatory authorities when approving new drugs.Methods. We present here a review of the literature.Results. A wide heterogeneity in the action of the various antidepressants precludes any single theory about the pathogenesis and therapy of depression. Antidepressant activity, in fact, may be achieved by acting on a number of different monoaminergic mechanisms. The variety in the neurochemical effects of antidepressants is not reflected in clinical trials, which tend to stereotypy. In many cases clinical trials aim at demonstrating equivalence rather than differences in efficacy. Regulatory authorities should, therefore, pay attention in accepting the equivalence of effects of a new drug in relation to a reference one: most clinical trials of new antidepressant drugs do not have the power to detect clinically relevant differences.Conclusions. Unconventional new pre-clinical tests are needed to generate antidepressants with a different mechanism of action. Clinical studies are needed to promote objective comparative evaluation of the cost, benefits and toxic effects of new antidepressants.
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Murawiec, Sławomir, and Marek Krzystanek. "Symptom Cluster-Matching Antidepressant Treatment: A Case Series Pilot Study." Pharmaceuticals 14, no. 6 (May 31, 2021): 526. http://dx.doi.org/10.3390/ph14060526.
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Despite treating depression with antidepressants, their effectiveness is often insufficient. Comparative effectiveness studies and meta-analyses show the effectiveness of antidepressants; however, they do not provide clear indications as to the choice of a specific antidepressant. The rational choice of antidepressants may be based on matching their mechanisms of action to the symptomatic profiles of depression, reflecting the heterogeneity of symptoms in different patients. The authors presented a series of cases of patients diagnosed with depression in whom at least one previous antidepressant treatment was shown to be ineffective before drug targeted symptom cluster-matching treatment (SCMT). The presented pilot study shows for the first time the effectiveness of SCMT in the different clusters of depressive symptoms. All the described patients obtained recovery from depressive symptoms after introducing drug-targeted SCMT. Once validated in clinical trials, SCMT might become an effective and rational method of selecting an antidepressant according to the individual profile of depressive symptoms, the mechanism of their formation, and the mechanism of drug action. Although the study results are preliminary, SCMT can be a way to personalize treatment, increasing the likelihood of improvement even in patients who meet criteria for treatment-resistant depression.
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Thase, Michael E. "New medications for treatment-resistant depression: a brief review of recent developments." CNS Spectrums 22, S1 (December 2017): 39–48. http://dx.doi.org/10.1017/s1092852917000876.
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There is a great unmet need for new medications with novel mechanisms of action that can effectively treat patients who do not benefit from standard antidepressant therapies. After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine. This article briefly highlights more recent research on ketamine and other investigational antidepressants.
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Borowicz-Reutt, Kinga K. "How Antidepressant Drugs Affect the Antielectroshock Action of Antiseizure Drugs in Mice: A Critical Review." International Journal of Molecular Sciences 22, no. 5 (March 3, 2021): 2521. http://dx.doi.org/10.3390/ijms22052521.
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Depression coexists with epilepsy, worsening its course. Treatment of the two diseases enables the possibility of interactions between antidepressant and antiepileptic drugs. The aim of this review was to analyze such interactions in one animal seizure model—the maximal electroshock (MES) in mice. Although numerous antidepressants showed an anticonvulsant action, mianserin exhibited a proconvulsant effect against electroconvulsions. In most cases, antidepressants potentiated or remained ineffective in relation to the antielectroshock action of classical antiepileptic drugs. However, mianserin and trazodone reduced the action of valproate, phenytoin, and carbamazepine against the MES test. Antiseizure drug effects were potentiated by all groups of antidepressants independently of their mechanisms of action. Therefore, other factors, including brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) modulation, should be considered as the background for the effect of drug combinations.
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Ochi, Taichi, Natalya M. Vyalova, Innokentiy S. Losenkov, Diana Z. Paderina, Ivan V. Pozhidaev, Anton J. M. Loonen, German G. Simutkin, Nikolay A. Bokhan, Bob Wilffert, and Svetlana A. Ivanova. "Preliminary Pharmacogenetic Study to Explore Putative Dopaminergic Mechanisms of Antidepressant Action." Journal of Personalized Medicine 11, no. 8 (July 27, 2021): 731. http://dx.doi.org/10.3390/jpm11080731.
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Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used to establish treatment response. HAMD 17 score status was measured before initiation, after two weeks, and after four weeks of treatment with various antidepressants. The possible association between response and genotype in a total of 14 variants of dopamine neurotransmission-related proteins was investigated. Results: DRD4 rs11246226 CA heterozygous patients were found with a greater improvement of HAMD 17 score when compared to homozygous C patients during 0–2 weeks and 0–4 weeks. Patients with MAOB rs1799836 heterozygous GA and homozygous A also demonstrated improved scores during 2–4 weeks and 0–4 weeks. Conclusions: The results are preliminary due to the limited population size and the small number of variants. Further research into the involvement of habenular dopamine D4 receptors in the antidepressant response is desirable.
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Dabetić, Marija, Milica Nešić, Uroš Dabetić, and Milan Latas. "Antidepressants and COVID-19: A case report and review of the literature." Engrami 44, no. 1 (2022): 89–99. http://dx.doi.org/10.5937/engrami43-39941.
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Introduction. Anti-inflammatory potential of antidepressants was observed before the COVID-19 pandemic. However, it recently regained spotlight when studies with large number of patients showed that antidepressants reduced the risk of intubation and death in COVID-19 symptomatic infection. Also, the response to antidepressants seems to be more rapid in post-COVID depression that in non-COVID19 related depression. The aim of this paper to review the literature regarding the effects and mechanisms of action of antidepressants in COVID-19 infection and post-COVID sequalae, and to present a case repot of a typical outpatient with post-COVID depression. Conclusion. Post-COVID depression is a common sequela of COVID-19 infection. Selective serotonin reuptake inhibitors elicit a rapid and efficient response in patients with post-COVID depression, which may be explained by their anti-inflammatory properties. Timely screening and treatment of post-COVID psychiatric disorders can significantly decrease the burden of COVID-19 pandemic both at the individual and societal level. Also, it is discussed how the pandemic studies of antidepressant mechanisms of actions provided new insights on the aetiology of depression.
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Frazer, A. "P.1.045 Mechanisms of action of antidepressants." European Neuropsychopharmacology 7 (September 1997): S149. http://dx.doi.org/10.1016/s0924-977x(97)88494-5.
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Shin, Cheolmin, and Yong-Ku Kim. "Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives." Psychiatry Investigation 17, no. 3 (March 25, 2020): 181–92. http://dx.doi.org/10.30773/pi.2019.0236.
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Major depressive disorder (MDD) is a serious psychiatric illness that causes functional impairment in many people. While monoaminergic antidepressants have been used to effectively treat MDD, these antidepressants have limitations in that they have delayed onset of action and many patients remain treatment-resistant. Therefore, there is a need to develop antidepressants with a novel target, and researchers have directed their attention to the glutamatergic system. Ketamine, although developed as an anesthetic, has been found to produce an antidepressant effect at sub-anesthetic doses via N-Methyl-D-aspartic acid (NMDA) receptor blockade as well as NMDA receptor- independent pathways. A single infusion of ketamine produced rapid improvement in clinical symptoms to a considerable level and led to the resolution of serious depressive symptoms, including imminent suicidal ideation, in patients with MDD. A series of recent randomized controlled trials have provided a high level of evidence for the therapeutic efficacy of ketamine treatment in MDD and presented new insights on the dose, usage, and route of administration of ketamine as an antidepressant. With this knowledge, it is expected that ketamine treatment protocols for MDD will be established as a treatment option available in clinical practice. However, long-term safety must be taken into consideration as ketamine has abuse potential and it is associated with psychological side effects such as dissociative or psychotomimetic effects.
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Leonard, Brian. "Clinical implications of mechanisms of action of antidepressants." Advances in Psychiatric Treatment 6, no. 3 (May 2000): 178–86. http://dx.doi.org/10.1192/apt.6.3.178.
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The purpose of this review is briefly to consider the biological basis of depression and to attempt to illustrate how antidepressants produce their beneficial effects by correcting these abnormalities.
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Vazagaeva, Tamara I., Roman V. Akhapkin, and Yuri A. Alexandrovsky. "The Role of Brain-Derived Neurotrophic Factor in Mediating the Action of Antidepressants in the Treatment of Depression." Annals of the Russian academy of medical sciences 74, no. 1 (April 3, 2019): 20–28. http://dx.doi.org/10.15690/vramn1107.
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According to the neurotrophic hypothesis of depression proposed two decades ago, the most important role in the pathogenesis of depressive disorders is played by abnormalities in the maintenance of neuronal plasticity regulated by brain neurotrophic factor (BDNF). Although the decline in BDNF activity in depression is now widely documented, it remains unclear whether it is a factor contributing to the onset of depression, or a consequence of the chronic course of the disease. In preclinical studies, it was found that exogenous BDNF infusions causes antidepressant-like effects, prevents the depressogenic effects of chronic stress and increases cell survival in the hippocampus and the prefrontal cortex, but the mechanisms mediating these effects have not been fully studied. The results of molecular genetic studies confirmed that BDNF is essential in mediating the therapeutic effect of antidepressants, while the role of genetic polymorphisms in predicting antidepressant efficacy in depression remains uncertain. The mechanisms of action of monoaminergic antidepressants are related to their effect on the expression of BDNF and its TrkB receptor, however, apparently, the effect size varies for different drugs. Peripheral BDNF levels increase during treatment with antidepressants, and this increase is clearly observed only during the acute phase treatment of depression, but not during the period of maintenance therapy. The serum level of BDNF is a potentially useful marker for diagnosing depression and prediction of a therapeutic response.
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Ansseau, M. "The paradox of tianeptine." European Psychiatry 8, S2 (1993): 89s—93s. http://dx.doi.org/10.1017/s0924933800005447.
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SummaryThe classical biochemical hypothesis of depression posits a functional deficit in central neurotransmitter systems, particularly serotonin (5-HT) and/or noradrenaline. The major support for this theory was that antidepressants increase the amount of neurotransmitters in the synaptic cleft, by inhibiting reuptake mechanisms (tricyclics) or inhibiting enzymatic catabolism (MAOIs). The major role suggested for 5-HT in this theory led to the development of a large number of compounds which selectively inhibit 5-HT reuptake, such as fluvoxamine, fluoxetine, citalopram, sertraline, paroxetine, etc. Numerous clinical studies have demonstrated the antidepressant activity of such types of agents, supporting 5-HT deficit as the main origin of depression. Tianeptine is active in classical animal models of antidepressants. Its antidepressant efficacy has been established in controlled trials involving a large number of patients. Several biochemical studies however demonstrated that tianeptine induces in acute as well as in chronic conditions, a presynaptic increase of 5-HT reuptake, both in animal and human platelets and animal CNS. Therefore, as a 5-HT reuptake enhancer, tianeptine exhibits a mechanism of action totally opposite to 5-HT reuptake blockers such as fluoxetine but, paradoxically, both mechanisms of action are associated with a therapeutic activity in depressive disorders. Several hypotheses to explain these paradoxical findings and different methodologies to test them clinically are proposed.
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Jarończyk, Małgorzata, and Jarosław Walory. "Novel Molecular Targets of Antidepressants." Molecules 27, no. 2 (January 14, 2022): 533. http://dx.doi.org/10.3390/molecules27020533.
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Antidepressants target a variety of proteins in the central nervous system (CNS), the most important belonging to the family of G-protein coupled receptors and the family of neurotransmitter transporters. The increasing number of crystallographic structures of these proteins have significantly contributed to the knowledge of their mechanism of action, as well as to the design of new drugs. Several computational approaches such as molecular docking, molecular dynamics, and virtual screening are useful for elucidating the mechanism of drug action and are important for drug design. This review is a survey of molecular targets for antidepressants in the CNS and computer based strategies to discover novel compounds with antidepressant activity.
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Stahl, Stephen M. "Novel Therapeutics for Depression:L-methylfolate as a Trimonoamine Modulator and Antidepressant-Augmenting Agent." CNS Spectrums 12, no. 10 (October 2007): 739–44. http://dx.doi.org/10.1017/s1092852900015418.
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Folate deficiency may increase the risk of depression and reduce the action of antidepressants. Individuals with an inherited polymorphism that reduces the efficiency of folate formation may be at high risk for folate deficiency and for major depression. Antidepressant effects have been reported when antidepressants are augmented with folic acid, folinic acid, or the centrally active L-methylfolate (known formally as (6(S)-5-methyltetrahydrofolate [MTHF]), particularly in depressed patients with folate deficiency whose major depressive episodes have failed to respond to antidepressants. The putative mechanism of action of MTHF as an augmenting agent to antidepressants is that it acts as a trimonoamine modulator (TMM), enhancing the synthesis of the three monoamines: dopamine (DA), norepinephrine (NE), and serotonin (5-HT), resulting in a boost to the efficacy of antidepressants.
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Mariani, Nicole, James Everson, Carmine M. Pariante, and Alessandra Borsini. "Modulation of microglial activation by antidepressants." Journal of Psychopharmacology 36, no. 2 (January 29, 2022): 131–50. http://dx.doi.org/10.1177/02698811211069110.
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Background: Recent studies have suggested that microglial activation plays a key role in the pathogenesis of depression. In fact, neuroinflammation is associated with a phenotypic change of microglia, consisting of morphological differences, increased release of cytokines and oxidative stress products, which may contribute to the development and maintenance of depression. Antidepressants, including selective serotonin re-uptake inhibitors and serotonin–norepinephrine reuptake inhibitors, have been shown to act on the immune and oxidative stress mechanisms commonly found to be disrupted in depression. Thus, the inhibition of microglial activation may be one of the mechanisms through which they exert an antidepressant action. Aim: This is the first review summarising in vitro and ex vivo studies investigating the effects of different classes of antidepressants on microglia activation, by examining cellular changes and/or via measuring the production of immune and/or oxidative stress signalling molecules, in microglia models of neuroinflammation with either lipopolysaccharide (LPS) or cytokines. A total of 23 studies were identified, 18 using LPS stimulation and 5 using cytokines stimulation. Results: Overall, the studies show that antidepressants, such as selective serotonin re-uptake inhibitors, serotonin–norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants prevented microglial activation, including reduced microglial reactivity and decreased immune and oxidative stress products, in both models. However, specific antidepressants, such as bupropion and agomelatine did not prevent interferon-gamma (IFN-γ)-induced microglial activation; and for other antidepressants, including phenelzine, venlafaxine and sertraline, the results of different studies were inconsistent. Conclusions: Overall, results summarised in this review support the hypothesis that the action of at least certain classes of antidepressants may involve regulation of microglial activation, especially when in presence of increased levels of inflammation.
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Dimoula, Anna, Dimitrios Fotellis, Evmorfia Aivalioti, Dimitrios Delialis, Alexia Polissidis, Raphael Patras, Nikolaos Kokras, and Kimon Stamatelopoulos. "Off-Target Effects of Antidepressants on Vascular Function and Structure." Biomedicines 10, no. 1 (December 28, 2021): 56. http://dx.doi.org/10.3390/biomedicines10010056.
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Depression emerges as a risk factor for cardiovascular disease, and it is thought that successful antidepressant treatment may reduce such a risk. Therefore, antidepressant treatment embodies a potential preventive measure to reduce cardiovascular events in patients with depression. Accumulating evidence indicates that antidepressants have off-target effects on vascular dysfunction and in the early stages of atherosclerosis, which form the basis for cardiovascular disease (CVD) pathogenesis. In this context, we performed a thorough review of the evidence pertaining to the effects of different classes of antidepressant medications on hemodynamic and early atherosclerosis markers. The preclinical and clinical evidence reviewed revealed a preponderance of studies assessing selective serotonin reuptake inhibitors (SSRI), whereas other classes of antidepressants are less well-studied. Sufficient evidence supports a beneficial effect of SSRIs on vascular inflammation, endothelial function, arterial stiffening, and possibly delaying carotid atherosclerosis. In clinical studies, dissecting the hypothesized direct beneficial antidepressant effect of SSRIs on endothelial health from the global improvement upon remission of depression has proven to be difficult. However, preclinical studies armed with appropriate control groups provide evidence of molecular mechanisms linked to endothelial function that are indeed modulated by antidepressants. This suggests at least a partial direct action on vascular integrity. Further research on endothelial markers should focus on the effect of antidepressants on treatment responders versus non-responders in order to better ascertain the possible beneficial vascular effects of antidepressants, irrespective of the underlying course of depression.
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Mitsi, Vasiliki, Dimitra Terzi, Immanuel Purushothaman, Lefteris Manouras, Sevasti Gaspari, Rachael L. Neve, Maria Stratinaki, Jian Feng, Li Shen, and Venetia Zachariou. "RGS9-2–controlled adaptations in the striatum determine the onset of action and efficacy of antidepressants in neuropathic pain states." Proceedings of the National Academy of Sciences 112, no. 36 (August 24, 2015): E5088—E5097. http://dx.doi.org/10.1073/pnas.1504283112.
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The striatal protein Regulator of G-protein signaling 9-2 (RGS9-2) plays a key modulatory role in opioid, monoamine, and other G-protein–coupled receptor responses. Here, we use the murine spared-nerve injury model of neuropathic pain to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a brain region involved in mood, reward, and motivation, modulates the actions of tricyclic antidepressants (TCAs). Prevention of RGS9-2 action in the NAc increases the efficacy of the TCA desipramine and dramatically accelerates its onset of action. By controlling the activation of effector molecules by G protein α and βγ subunits, RGS9-2 affects several protein interactions, phosphoprotein levels, and the function of the epigenetic modifier histone deacetylase 5, which are important for TCA responsiveness. Furthermore, information from RNA-sequencing analysis reveals that RGS9-2 in the NAc affects the expression of many genes known to be involved in nociception, analgesia, and antidepressant drug actions. Our findings provide novel information on NAc-specific cellular mechanisms that mediate the actions of TCAs in neuropathic pain states.
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Nowakowska, E., K. Kus, and R. Chodera-Otuszewska. "Behavioural effects of two antidepressants with opposite action mechanisms." Biological Psychiatry 42, no. 1 (July 1997): 33S. http://dx.doi.org/10.1016/s0006-3223(97)87007-2.
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Palaniyappan, Lena, and R. Hamish McAllister-Williams. "Antidepressants: will new mechanisms of action improve poor outcomes?" British Journal of Hospital Medicine 69, no. 2 (February 2008): 88–90. http://dx.doi.org/10.12968/hmed.2008.69.2.28353.
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McHugh, Patrick C., Geraldine R. Rogers, Dylan M. Glubb, Melanie D. Allington, Mark Hughes, Peter R. Joyce, and Martin A. Kennedy. "Downregulation ofCcnd1andHes6in rat hippocampus after chronic exposure to the antidepressant paroxetine." Acta Neuropsychiatrica 20, no. 6 (December 2008): 307–13. http://dx.doi.org/10.1111/j.1601-5215.2008.00334.x.
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Objective:The mechanism of action of antidepressant drugs is not fully understood. Application of genomic methods enables the identification of biochemical pathways that are regulated by antidepressants, and this may provide novel clues to the molecular and cellular actions of these drugs. The present study examined gene expression profiles in the hippocampus of rats exposed to chronic antidepressant treatment.Methods:Animals were treated for 12 days with the selective serotonin reuptake inhibitor paroxetine; then, hippocampal ribonucleic acid was recovered, and changes in gene expression were assessed by microarray analysis.Results:A total of 160 genes that showed differential expression after paroxetine exposure were identified. Using functional relevance and observed fold change as selection criteria, the expression changes in a subset of these genes were confirmed by quantitative polymerase chain reaction.Conclusion:Of this subset, only two genes, cyclin D1 (Ccnd1) and hairy and enhancer of split 6 (Hes6), showed robust and consistent changes in expression. Both genes were downregulated by paroxetine, and both have been previously implicated in neurogenesis. Further investigation of these two genes may provide new insight into the mechanism of action of antidepressants.
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Matveychuk, Dmitriy, Rejish K. Thomas, Jennifer Swainson, Atul Khullar, Mary-Anne MacKay, Glen B. Baker, and Serdar M. Dursun. "Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers." Therapeutic Advances in Psychopharmacology 10 (January 2020): 204512532091665. http://dx.doi.org/10.1177/2045125320916657.
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Ketamine, a drug introduced in the 1960s as an anesthetic agent and still used for that purpose, has garnered marked interest over the past two decades as an emerging treatment for major depressive disorder. With increasing evidence of its efficacy in treatment-resistant depression and its potential anti-suicidal action, a great deal of investigation has been conducted on elucidating ketamine’s effects on the brain. Of particular interest and therapeutic potential is the ability of ketamine to exert rapid antidepressant properties as early as several hours after administration. This is in stark contrast to the delayed effects observed with traditional antidepressants, often requiring several weeks of therapy for a clinical response. Furthermore, ketamine appears to have a unique mechanism of action involving glutamate modulation via actions at the N-methyl-D-aspartate (NMDA) and [Formula: see text]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as downstream activation of brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR) signaling pathways to potentiate synaptic plasticity. This paper provides a brief overview of ketamine with regard to pharmacology/pharmacokinetics, toxicology, the current state of clinical trials on depression, postulated antidepressant mechanisms and potential biomarkers (biochemical, inflammatory, metabolic, neuroimaging sleep-related and cognitive) for predicting response to and/or monitoring of therapeutic outcome with ketamine.
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Preskorn, S. "Pharmacotherapeutic profile of venlafaxine." European Psychiatry 12, S4 (1997): 285s—294s. http://dx.doi.org/10.1016/s0924-9338(97)83307-x.
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SummaryWhen selecting an antidepressant, a number of factors must be considered. These considerations are summarized under the mnemonic STEPS: Safety, Tolerability, Efficacy, Payment (eg, cost-effectiveness), and Simplicity of use. Venlafaxine is the first of a new class of antidepressants that selectively blocks the serotonin and noradrenaline uptake pumps without blocking muscarinic, histaminergic and adrenergic receptors or inhibiting sodium fast channels. Because venlafaxine avoids these mechanisms of action, it has a wide therapeutic index, an improved tolerability profile and a reduced risk of causing pharmacodynamically mediated drug-drug interactions when compared to tricyclic antidepressants (TCAs). In contrast to some other new antidepressants, venlafaxine also avoids effects on cytochrome P450 which are likely to cause clinically meaningful, pharmacokinetically mediated drug-drug interactions. The effects on the uptake pumps of both serotonin and noradrenaline appear to be responsible for some of venlafaxine's unique features in terms of antidepressant efficacy, including its ascending antidepressant dose-response curve and its apparent rapid onset of antidepressant action at the upper end of its clinically relevant dosing range. Venlafaxine is effective in a broad spectrum of patients, including outpatients and inpatients, those with and without melancholia, patients with symptoms of anxiety or agitation or retardation and patients with first time or recurrent episodes of major depression. An important factor when selecting an antidepressant is the simplicity of the dosing regimen and the ability to rapidly and confidently achieve the optimal dose for the patient. In this regard, venlafaxine can be initiated at a clinically effective dose from the beginning. If the patient fails to respond to this dose, there is evidence that increased antidepressant efficacy can be achieved by increasing the dose rather than having to resort to an augmentation strategy or switch to another class of antidepressants. In the immediate release form, venlafaxine has proven antidepressant efficacy when using a twice-or three-times-a-day schedule. A sustained release formulation is expected to be marketed soon and will permit once-a-day-dosing.
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Frazer, Alan, and Audie L. Murphy. "MECHANISMS OF ACTIONS OF ANTIDEPRESSANTS." American Journal of Geriatric Psychiatry 7 (September 1999): 9. http://dx.doi.org/10.1097/00019442-199911001-00027.
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Wang, Shikai, Sufang Tang, Jintao Huang, and Huanxin Chen. "Rapid-acting antidepressants targeting modulation of the glutamatergic system: clinical and preclinical evidence and mechanisms." General Psychiatry 35, no. 6 (December 2022): e100922. http://dx.doi.org/10.1136/gpsych-2022-100922.
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Major depressive disorder (MDD) is a devastating mental illness that affects approximately 20% of the world’s population. It is a major disease that leads to disability and suicide, causing a severe burden among communities. Currently available medications for treating MDD target the monoaminergic systems. The most prescribed medications include selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. However, these medications have serious drawbacks, such as a delayed onset requiring weeks or months to reach efficacy and drug resistance, as one-third of patients are unresponsive to the medications. Therefore, it is imperative to develop novel therapies with rapid action, high efficacy and few adverse effects. The discovery of the rapid antidepressant effect of ketamine has triggered tremendous enthusiasm for studying new antidepressants that target the glutamatergic system in the central nervous system. Many agents that directly or indirectly modulate the glutamatergic system have been shown to provide rapid and lasting antidepressant action. Among these agents, ketamine, an antagonist of metabotropic glutamate 2/3 receptors, and scopolamine, an unspecific muscarinic acetylcholine receptor antagonist, have been extensively studied. In this review, we discuss the clinical and preclinical evidence supporting the antidepressant efficacy of these agents and the current understanding of the underlying mechanisms.
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Kuznetsov, Yu V., D. V. Evdokimov, and I. I. Abramets. "The new molecular targets for antidepressants." Medical Herald of the South of Russia 12, no. 1 (March 29, 2021): 24–32. http://dx.doi.org/10.21886/2219-8075-2021-12-1-24-32.
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The efficacy of depressive disorders treatment is insufficient. It is explained by an incomplete understanding of both pathogenesis of depression and antidepressants mechanism action. An improvement of the treatment efficacy of depression disorders is closely associated with complete knowledge of the pathogenesis of disorders and antidepressant mechanism of action. The effect produced by the first line of antidepressants prescribed currently in the clinical practice includes the accumulation of monoamines and prolonged activation of their membrane receptors. However, a decrease in the membrane receptors density evoked by prolonged activation of monoaminergic receptors is counteracted by the second line of antidepressant activity. It is associated with the expression of inducible regulatory protein S100A10 (p11) and its partners. In this review, the authors examined the structure and function of protein p11, its interaction with such proteins as annexin A2, Ahnak, chromatinremodeling factor SMARCA3. The authors analyzed the influence of p11 on the membrane density of serotonin 5-HT1B and 5-HT4 receptors, metabotropic glutamate receptors 5, voltage-dependent potassium Kv3, and calcium Cav1.2 and 1.3 channels, that play an important role in both the effect of antidepressants and the pathogenesis of depression disorders. A systematic literature search was conducted in Scopus, Web of Science, MedLine, elibrary, and other databases.
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Martucci, N., V. Manna, and A. Agnoli. "Antidepressant Drugs and Migraine." Cephalalgia 5, no. 2_suppl (May 1985): 225–28. http://dx.doi.org/10.1177/03331024850050s244.
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There is evidence that some antidepressant drugs, above all amitriptyline and mianserine, are beneficial in the prophylaxis of migraine. The mechanism of action of antidepressants in migraine is likely to be complex. Mood disturbances accompanying migraine syndromes suggest a mode of action of such a class of drugs. In the last few years some clinical studies tend to show that the antimigraine effects of these drugs seem relatively independent of the antidepressant activity.
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Norman, Trevor R. "Experimental and Clinical Pharmacology: The new antidepressants - mechanisms of action." Australian Prescriber 22, no. 5 (October 1, 1999): 106–8. http://dx.doi.org/10.18773/austprescr.1999.094.
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Andreeva, N. I. "Pharmacological properties and mechanisms of action of new antidepressants (review)." Pharmaceutical Chemistry Journal 27, no. 7 (July 1993): 453–63. http://dx.doi.org/10.1007/bf00780195.
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Hen-Shoval, Danielle, Aron Weller, Abraham Weizman, and Gal Shoval. "Examining the Use of Antidepressants for Adolescents with Depression/Anxiety Who Regularly Use Cannabis: A Narrative Review." International Journal of Environmental Research and Public Health 19, no. 1 (January 4, 2022): 523. http://dx.doi.org/10.3390/ijerph19010523.
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Depression and anxiety disorders are two of the most common and growing mental health concerns in adolescents. Consequently, antidepressant medication (AD) use has increased widely during the last decades. Several classes of antidepressants are used mainly to treat depression, anxiety, and obsessive-compulsive disorders by targeting relevant brain neurochemical pathways. Almost all randomized clinical trials of antidepressants examined patients with no concomitant medications or drugs. This does not address the expected course of therapy and outcome in cannabis users. Cannabis is the most commonly used illicit substance globally. Substantial changes in its regulation are recently taking place. Many countries and US states are becoming more permissive towards its medical and recreational use. The psychological and physiological effects of cannabis (mainly of its major components, tetrahydrocannabinol (THC) and cannabidiol (CBD)) have been extensively characterized. Cannabis use can be a risk factor for depressive and anxiety symptoms, but some constituents or mixtures may have antidepressant and/or anxiolytic potential. The aim of this literature review is to explore whether simultaneous use of AD and cannabis in adolescence can affect AD treatment outcomes. Based on the current literature, it is reasonable to assume that antidepressants are less effective for adolescents with depression/anxiety who frequently use cannabis. The mechanisms of action of antidepressants and cannabis point to several similarities and conjunctions that merit future investigation regarding the potential effectiveness of antidepressants among adolescents who consume cannabis regularly.
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Catena-Dell'Osso, Mario, Andrea Fagiolini, Francesco Rotella, Stefano Baroni, and Donatella Marazziti. "Glutamate system as target for development of novel antidepressants." CNS Spectrums 18, no. 4 (February 1, 2013): 188–98. http://dx.doi.org/10.1017/s1092852912000971.
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Depression is a common psychiatric condition characterized by affective, cognitive, psychomotor, and neurovegetative symptoms that interfere with a person's ability to work, study, deal with interpersonal relationships, and enjoy once-pleasurable activities. After the serendipitous discovery of the first antidepressants, for years the only pharmacodynamic mechanisms explored in the search of novel antidepressants were those related to the 3 main monoamines: serotonin, norepinephrine, and dopamine. New-generation monoaminergic antidepressants, such as selective-serotonin and dual-acting serotonin/norepinephrine reuptake inhibitors, improved treatment and quality of life of depressed patients. Nevertheless, there are still important clinical limitations: the long latency of onset of the antidepressant action; side effects, which can lead to early discontinuation; low rate of response; and high rate of relapse/recurrence. Therefore, in the last several years, the focus of research has moved from monoamines toward other molecular mechanisms, including glutamatergic (Glu) neurotransmission. This review provides a comprehensive overview of the current knowledge on the Glu system and on its relationships with mood disorders. Up to now, N-methyl-D-aspartate (NMDA) receptor antagonists, in particular ketamine, provided the most promising results in preclinical studies and produced a consistent and rapid, although transient, antidepressant effect with a good tolerability profile in humans. Although data are encouraging, more double-blind, randomized, placebo-controlled trials are needed to clarify the real potentiality of ketamine, and of the other Glu modulators, in the treatment of unipolar and bipolar depression.
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Mateus, M., G. P. da Silva Borges, C. Silva, and F. Lourenço. "ERKs - a New Marker in Psychiatry?" European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70785-0.
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Recent studies involved the pathways of kinases regulated by extracellular signal (ERK - extracellular signal regulated kinases), a broad range of key cellular processes, in the mechanisms of depression and consequently in the action of antidepressants. It is also known that the use of specific inhibitors of phosphorylation of ERKs1 / 2 showed to have antidepressant effect in animal models. Fluoxetina (SSRI) was recently discovered to be a potente inhibitor of phosphorylation of ERKs. The ERKs1 / 2 and recently the 3, are present in neurons and glia, these also engaged in biological mechanisms of depression.The authors propose to do, based on the current literature, the characterization of the type (s) of cell (s) where changes in activation of ERKs1 / 2, occur during depression, and during the administration of antidepressants, in order to understand, to what extent these kinases may be considered as biological markers of depression. Possibly also to examine the feasibility of using these markers in clinical use.
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Hesselgrave, Natalie, Timothy A. Troppoli, Andreas B. Wulff, Anthony B. Cole, and Scott M. Thompson. "Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice." Proceedings of the National Academy of Sciences 118, no. 17 (April 13, 2021): e2022489118. http://dx.doi.org/10.1073/pnas.2022489118.
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Depression is a widespread and devastating mental illness and the search for rapid-acting antidepressants remains critical. There is now exciting evidence that the psychedelic compound psilocybin produces not only powerful alterations of consciousness, but also rapid and persistent antidepressant effects. How psilocybin exerts its therapeutic actions is not known, but it is widely presumed that these actions require altered consciousness, which is known to be dependent on serotonin 2A receptor (5-HT2AR) activation. This hypothesis has never been tested, however. We therefore asked whether psilocybin would exert antidepressant-like responses in mice and, if so, whether these responses required 5-HT2AR activation. Using chronically stressed male mice, we observed that a single injection of psilocybin reversed anhedonic responses assessed with the sucrose preference and female urine preference tests. The antianhedonic response to psilocybin was accompanied by a strengthening of excitatory synapses in the hippocampus—a characteristic of traditional and fast-acting antidepressants. Neither behavioral nor electrophysiological responses to psilocybin were prevented by pretreatment with the 5-HT2A/2C antagonist ketanserin, despite positive evidence of ketanserin’s efficacy. We conclude that psilocybin’s mechanism of antidepressant action can be studied in animal models and suggest that altered perception may not be required for its antidepressant effects. We further suggest that a 5-HT2AR–independent restoration of synaptic strength in cortico-mesolimbic reward circuits may contribute to its antidepressant action. The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression.
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Ciubara, Anamaria, Roxana Chirita, Gabriela Paduraru, Dania Andreea Radu, Claudia Adriana Olaru, Ilinca Untu, and Lucian Stefan Burlea. "The psychosocial impact of chronic abdominal pain in functional gastrointestinal disorders for both children and adolescents – clinical and therapeutic approaches." Romanian Journal of Pediatrics 63, no. 3 (September 30, 2014): 229–32. http://dx.doi.org/10.37897/rjp.2014.3.1.
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Both functional abdominal pain and irritable bowel syndrome are common causes of chronic abdominal pain in children and adolescents. Addressing these nosological entities is done according to the biopsychosocial model of functional gastrointestinal disorders, given their effect on quality of life and psychosocial status thereof. The cognitive-behavioral therapy, family psychotherapy, relaxation techniques or hypnotherapy have proved effective in achieving better coping mechanisms in alleviating psychological and somatic symptoms. However, antidepressant medication including selective serotonin reuptake inhibitors and tricyclic antidepressants, improve psychiatric symptomatology, especially depressive mood due to gastrointestinal illness, but also digestive symptoms due to mechanisms of action that depend on complex neurotransmitters.
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Richelson, Elliott. "Multi-modality: a new approach for the treatment of major depressive disorder." International Journal of Neuropsychopharmacology 16, no. 6 (July 1, 2013): 1433–42. http://dx.doi.org/10.1017/s1461145712001605.
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Abstract Effective treatment with antidepressants is currently limited by factors that affect treatment compliance, including delay in onset of therapeutic effects and intolerable side-effects. Recent data suggest that use of antidepressant combinations with different mechanisms of action may be a better first-line strategy prior to augmentation with other drug classes. The rationale for this approach is that combining multiple pharmacological actions affecting multiple monoamine targets produces greater efficacy. Several new multi-modal compounds are in development and early results for the most advanced agents indicate shorter onset of therapeutic effects and improved tolerability. By modulating multiple receptors and transmitter systems, it is hoped that these new agents may also treat some of the associated symptoms of major depressive disorder, such as anxiety and cognitive dysfunction.
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Haarsma, Joost, Catherine J. Harmer, and Sandra Tamm. "A continuum hypothesis of psychotomimetic rapid antidepressants." Brain and Neuroscience Advances 5 (January 2021): 239821282110077. http://dx.doi.org/10.1177/23982128211007772.
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Ketamine, classical psychedelics and sleep deprivation are associated with rapid effects on depression. Interestingly, these interventions also have common psychotomimetic actions, mirroring aspects of psychosis such as an altered sense of self, perceptual distortions and distorted thinking. This raises the question whether these interventions might be acute antidepressants through the same mechanisms that underlie some of their psychotomimetic effects. That is, perhaps some symptoms of depression can be understood as occupying the opposite end of a spectrum where elements of psychosis can be found on the other side. This review aims at reviewing the evidence underlying a proposed continuum hypothesis of psychotomimetic rapid antidepressants, suggesting that a range of psychotomimetic interventions are also acute antidepressants as well as trying to explain these common features in a hierarchical predictive coding framework, where we hypothesise that these interventions share a common mechanism by increasing the flexibility of prior expectations. Neurobiological mechanisms at play and the role of different neuromodulatory systems affected by these interventions and their role in controlling the precision of prior expectations and new sensory evidence will be reviewed. The proposed hypothesis will also be discussed in relation to other existing theories of antidepressants. We also suggest a number of novel experiments to test the hypothesis and highlight research areas that could provide further insights, in the hope to better understand the acute antidepressant properties of these interventions.
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Zimmermann, Nicole, Jürgen Zschocke, Tatjana Perisic, Shuang Yu, Florian Holsboer, and Theo Rein. "Antidepressants inhibit DNA methyltransferase 1 through reducing G9a levels." Biochemical Journal 448, no. 1 (October 18, 2012): 93–102. http://dx.doi.org/10.1042/bj20120674.
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The discovery of epigenetic processes as possible pivotal regulatory mechanisms in psychiatric diseases raised the question of how psychoactive drugs may impact the epigenetic machinery. In the present study we set out to explore the specificity and the mode of action of the reported inhibitory effect of the TCA (tricyclic antidepressant) amitriptyline on DNMT (DNA methyltransferase) activity in primary astrocytes from the rat cortex. We found that the impact on DNMT was shared by another TCA, imipramine, and by paroxetine, but not by venlafaxine or the mood stabilizers carbamazepine and valproic acid. DNMT activity in subventricular neural stem cells was refractory to the action of ADs (antidepressants). Among the established DNMTs, ADs primarily targeted DNMT1. The reduction of enzymatic DNMT1 activity was neither due to reduced DNMT1 expression nor due to direct drug interference. We tested putative DNMT1-inhibitory mechanisms and discovered that a known stimulator of DNMT1, the histone methyltransferase G9a, exhibited decreased protein levels and interactions with DNMT1 upon AD exposure. Adding recombinant G9a completely reversed the AD repressive effect on DNMT1 function. In conclusion, the present study presents a model where distinct ADs affect DNMT1 activity via G9a with important repercussions for possible novel treatment regimes.
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Álvarez Silva, Adriana, and Alonso Fernández-Guasti. "Does the antidepressant-like effect of mirtazapine and venlafaxine differ between male and female rats?" Salud mental 43, no. 1 (January 30, 2020): 3–9. http://dx.doi.org/10.17711/sm.0185-3325.2020.002.
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Introduction. Depression is a global health problem with nearly 350 million people affected, mainly women. However, nowadays a rising amount of men are being diagnosed. This makes necessary the screening of new treatment options that are effective in women as well as in men. Objective. To analyze if the administration of mirtazapine and venlafaxine to male and female rats shows a sex-related antidepressant-like effect, and the possible associated neurochemical mechanisms. Method. Mirtazapine (40 mg/kg) or venlafaxine (60 mg/kg) were administered subchronically to young adult male and female (ovariectomized and steroid-primed) rats, and their antidepressant-like effects were evaluated using the forced swim test (FST). The active behaviors, swimming and climbing, were also analyzed. Results. a) mirtazapine and venlafaxine reduced immobility in the FST in males and females; b) both antidepressants increased climbing and swimming in male rats; c) in female rats, mirtazapine and venlafaxine only increased swimming. Discussion and conclusion. In males, the effects of mirtazapine and venlafaxine seem to be produced by the activation of the serotonergic and noradrenergic systems. Conversely, estradiol might be modulating the mechanisms of action of both antidepressants in females producing only an increased swimming and suggesting the participation of the serotonergic system.
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Taylor, Chirisse, Ashwana D. Fricker, Lakshmi A. Devi, and Ivone Gomes. "Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways." Cellular Signalling 17, no. 5 (May 2005): 549–57. http://dx.doi.org/10.1016/j.cellsig.2004.12.007.
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Alqarni, Turky Ali, Jamilah Abdullah Alruwaili, Basil Fahad Almutairi, Aishah Khalaf Hawas Alanazi, Wedad Mohammad Alotaibi, Mohammed Abdullah Meeteq, Wansah sudi alroiley, and Radhwa Dawood Mohamed Alanazi. "Treat Clinical Depression Using Antidepressants." International Journal Of Pharmaceutical And Bio-Medical Science 02, no. 12 (December 9, 2022): 586–91. http://dx.doi.org/10.47191/ijpbms/v2-i12-02.
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SSRIs are chemically distinct from traditional antidepressants such as tricyclic, tetracyclic, and monoamine oxidase inhibitors, but they share the same mechanism of action in that they selectively and potently inhibit serotonin neuronal reuptake while having no or very little effect on norepinephrine, acetylcholine, and histamine neuronal reuptake. As a result, when compared to other tricyclic and tetracyclic antidepressants, these drugs have fewer sedative, anticholinergic, and cardiovascular effects. Fluroxamine, fluroxamine, sertraline, indalpine, paroxetine, alproclate, femorxetine, and choroxamine are examples of SSRI drugs.
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Koncz, Szabolcs, Noémi Papp, Noémi Menczelesz, Dóra Pothorszki, and György Bagdy. "EEG and Sleep Effects of Tramadol Suggest Potential Antidepressant Effects with Different Mechanisms of Action." Pharmaceuticals 14, no. 5 (May 4, 2021): 431. http://dx.doi.org/10.3390/ph14050431.
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Tramadol is a widely used, centrally acting, opioid analgesic compound, with additional inhibitory effects on the synaptic reuptake of serotonin and noradrenaline, as well as on the 5-HT2 and NMDA receptors. Preclinical and clinical evidence also suggests its therapeutic potential in the treatment of depression and anxiety. The effects of most widely used antidepressants on sleep and quantitative electroencephalogram (qEEG) are well characterized; however, such studies of tramadol are scarce. Our aim was to characterize the effects of tramadol on sleep architecture and qEEG in different sleep–wake stages. EEG-equipped Wistar rats were treated with tramadol (0, 5, 15 and 45 mg/kg) at the beginning of the passive phase, and EEG, electromyogram and motor activity were recorded. Tramadol dose-dependently reduced the time spent in rapid eye movement (REM) sleep and increased the REM onset latency. Lower doses of tramadol had wake-promoting effects in the first hours, while 45 mg/kg of tramadol promoted sleep first, but induced wakefulness thereafter. During non-REM sleep, tramadol (15 and 45 mg/kg) increased delta and decreased alpha power, while all doses increased gamma power. In conclusion, the sleep-related and qEEG effects of tramadol suggest antidepressant-like properties, including specific beneficial effects in selected patient groups, and raise the possibility of a faster acting antidepressant action.
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Behr, Guilherme A., José C. F. Moreira, and Benicio N. Frey. "Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder." Oxidative Medicine and Cellular Longevity 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/609421.
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Major depressive disorder (MDD) is a common mental disorder associated with a significant negative impact on quality of life, morbidity/mortality, and cognitive function. Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials and reduced brain GSH levels. Also, F2-isoprostanes circulatory levels are increased in MDD subjects and are correlated with the severity of depressive symptoms. Urinary excretion of 8-OHdG seems to be higher in patients with MDD compared to healthy controls. Despite the fact that antidepressant drugs have been used for more than 50 years, their mechanism of action is still not fully understood. This paper examines preclinical (in vitroand animal model) and clinical literature on oxidative/antioxidant effects associated with antidepressant agents and discusses their potential antioxidant-related effects in the treatment of MDD. Substantial data support that MDD seems to be accompanied by elevated levels of oxidative stress and that antidepressant treatments may reduce oxidative stress. These studies suggest that augmentation of antioxidant defences may be one of the mechanisms underlying the neuroprotective effects of antidepressants in the treatment of MDD.
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Gulsun, Murat, Ayhan Algul, Umit Basar Semiz, Mehmet Alpay Ates, Ali Doruk, Servet Ebrinc, Cengiz Basoglu, and Mesut Cetin. "A Case with Euprolactinemic Galactorrhea Induced by Escitalopram." International Journal of Psychiatry in Medicine 37, no. 3 (September 2007): 275–78. http://dx.doi.org/10.2190/pm.37.3.d.
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Endocrine and reproductive side effects of serotonergic antidepressants are uncommon and galactorrhea is only rarely mentioned among SSRI-related side effects. Perhaps through suppression of dopamine neurotransmission releasing prolactin from tonic inhibitor control of dopamine, serotonin-enhancing antidepressants may result in a rise in prolactin levels. However, we here describe a case of euprolactinemic galactorrhea induced by the SSRI escitalopram and discuss potential mechanisms of action.
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Pérez-Esparza, Rodrigo, Luis Fabián Kobayashi-Romero, Ana María García Mendoza, Reyna Minerva Lamas-Aguilar, Melissa Vargas Sosa, Melissa Encarnación-Martínez, Luz Andrea González-Manríquez, et al. "Ketamina, un nuevo agente terapéutico para la depresión." Revista de la Facultad de Medicina 63, no. 1 (January 10, 2020): 6–13. http://dx.doi.org/10.22201/fm.24484865e.2020.63.1.02.
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Major depressive disorder affects about one in every 10 people in Mexico and is one of the first 5 causes of disability worldwide. Current treatment options are limited and only act upon some factors associated in its physiopathology. Moreover, the effects on depression are not immediate, which is a great limitation in obtaining a benefit over disability caused by this disorder and impedes a rapid action in the scenario of suicidality. Recently, ketamine (an anesthetic) has shown to have antidepressant properties by acting in the glutamate neurotransmission system (while no other current treatment acts on this level). It offers benefits in depressive symptoms in a matter of hours and has proven to be useful in patients that do not benefit from current therapeutic options. Recently, it has been approved for the treatment of depression. However, there are still many questions about its antidepressant mechanisms of action, safety, side effects, among others. Key words: Depression; antidepressants; ketamine.
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Leuchter, Andrew F., Ian A. Cook, David J. DeBrota, Aimee M. Hunter, William Z. Potter, Caroline C. McGrouther, Melinda L. Morgan, Michelle Abrams, and Barbara Siegman. "Changes in Brain Function during Administration of Venlafaxine or Placebo to Normal Subjects." Clinical EEG and Neuroscience 39, no. 4 (October 2008): 175–81. http://dx.doi.org/10.1177/155005940803900405.
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Previous research has demonstrated neurophysiologic effects of antidepressants in depressed subjects. We evaluated neurophysiologic effects of venlafaxine in normal subjects. Healthy adults (n=32) received a 1-week placebo lead-in followed by 4 weeks randomized double-blind treatment with venlafaxine IR 150 mg. (n = 17) or placebo (n = 15). Brain function was examined using quantitative electroencephalographic (QEEG) power and theta cordance. Normal subjects receiving venlafaxine showed a decrease in theta-band cordance in the midline-and-right-frontal (MRF) region at 48 hours and at 1 week after randomization. Decreases in relative power also were seen in the MRF region; there were no significant changes in absolute power. These changes were significantly different from those in subjects receiving placebo. Changes in MRF cordance accurately identified treatment condition at 48 hours in 81.3% of subjects, and relative power from this region identified 60.7% of subjects. In conclusion, cordance may detect the pharmacological effects of antidepressant medication in normal subjects. Future studies should examine other classes of medication, as well as antidepressants with other mechanisms of action, to determine if cordance detects antidepressant medication effects in general in normal subjects.
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Wasielewska, Magdalena. "Comparison of the mechanisms of action of antidepressants and their side effects." Journal of Education, Health and Sport 10, no. 8 (August 20, 2020): 260. http://dx.doi.org/10.12775/jehs.2020.10.08.030.
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Kedzierska, Ewa, and Izabela Wach. "Using tests and models to assess antidepressant-like activity in rodents." Current Issues in Pharmacy and Medical Sciences 29, no. 2 (June 1, 2016): 61–65. http://dx.doi.org/10.1515/cipms-2016-0013.
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Abstract In today's world, depression is one of the more prevalent forms of mental illness. According to WHO, about 10%-30% of all women and 7%-15% of all men are afflicted by depression at least once in their life-times. Today, depression is assessed to be affecting 350 million people. Regarding this issue, an important challenge for current psychopharmacology is to develop new, more effective pharmacotherapy and to understand the mechanism of action of known antidepressants. Furthermore, there is the necessity to improve the effectiveness of anti-depression treatment by way of bringing about an understanding of the neurobiology of this illness. In achieving these objectives, animal models of depression can be useful. Yet, presently, all available animal models of depression rely on two principles: the actions of known antidepressants or the responses to stress. In this paper, we present an overview of the most widely used animal tests and models that are employed in assessing antidepressant-like activity in rodents. These include amphetamine potentiation, reversal of reserpine action, the forced swimming test, the tail suspension test, learned helplessness, chronic mild stress and social defeat stress. Moreover, the advantages and major drawbacks of each model are also discussed.
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Gowda, Chandan R., and Leslie P. Lundt. "Mechanism of action of narcolepsy medications." CNS Spectrums 19, S1 (November 18, 2014): 25–34. http://dx.doi.org/10.1017/s1092852914000583.
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The medications used to treat narcolepsy are targeted toward alleviating symptoms such as excessive sleepiness and cataplexy. The cause of this neurological sleep disorder is still not completely clear, though a destruction of hypocretin/orexin neurons has been implicated. The destruction of these neurons is linked to inactivity of neurotransmitters including histamine, norepinephrine, acetylcholine, and serotonin, causing a disturbance in the sleep/wake cycles of narcoleptic patients. Stimulants and MAOIs have traditionally been used to counteract excessive daytime sleepiness and sleep attacks by inhibiting the breakdown of catecholamines. Newer drugs, called wake-promoting agents, have recently become first-line agents due to their better side-effect profile, efficacy, and lesser potential for abuse. These agents similarly inhibit reuptake of dopamine, but have a novel mechanism of action, as they have been found to increase neuronal activity in the tuberomamillary nucleus and in orexin neurons. Sodium oxybate, a sodium salt of gamma-hydroxybutyrate (GHB), is another class that is used to treat many symptoms of narcolepsy, and is the only U.S. Food and Drug Administration (FDA)-approved medication for cataplexy. It has a different mechanism of action than either stimulants or wake-promoting agents, as it binds to its own unique receptor. Antidepressants, like selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been used, as similar to stimulants, they inhibit reuptake of specific catecholamines. In this article, we seek to review the mechanisms behind these classes of drugs in relation to the proposed pathophysiology of narcolepsy. Appropriate clinical strategies will be discussed, including specific combinations of medications that have been shown to be effective.
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Golan, Moran, Gabriel Schreiber, and Sofia Avissar. "Antidepressant-induced differential ubiquitination of β-arrestins 1 and 2 in mononuclear leucocytes of patients with depression." International Journal of Neuropsychopharmacology 16, no. 8 (September 1, 2013): 1745–54. http://dx.doi.org/10.1017/s1461145713000291.
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Abstract β-Arrestins 1 and 2, cytosolic proteins known to mediate receptor desensitization, endocytosis and G protein-independent signalling, are post-translationally modified by ubiquitination regulating their ability to serve as adaptors and scaffolds. β-Arrestins were suggested to play a role in the pathophysiology of depression and in antidepressant mechanism of action. To determine whether a depressive episode or antidepressant treatment induce significant selective differences in β-arrestin 1 and 2 levels or their ubiquitination patterns in leucocytes of patients with depression, 46 outpatients diagnosed with a depressive episode were examined before and after 4-wk antidepressant treatment compared with age- and gender-matched control subjects. β-Arrestin levels were measured by immunoblotting using anti-arrestin antibodies. Ubiquitination of β-arrestins was measured using anti-ubiquitin antibodies followed by an immunoprecipitation step and immunoblotting using anti-arrestin antibodies. Antidepressants induced selective alterations in leucocyte β-arrestin 1 and 2 levels and ubiquitination. The levels of β-arrestin 1 and 2 and their ubiquitinated forms in leucocytes of yet untreated patients with depression were significantly decreased in a symptom severity correlated manner compared to control subjects. Antidepressants normalized β-arrestin 1 and 2 levels and uncovered novel differences between the two isoforms: (a) while antidepressants normalized ubiquitination of β-arrestin 1, ubiquination of β-arrestin 2 was unaffected; (b) while under antidepressants ubiquitination extent of β-arrestin 1 positively correlated with its level, an inverse picture of negative correlation was found between ubiquitination extent of β-arrestin 2 and its level. We conclude that antidepressants may serve as a tool to detect functional differences between the two β-arrestin isoforms and that through these differential effects antidepressants can induce specific alterations in alternative cellular signalling.