Academic literature on the topic 'NMDA receptor antagonists'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'NMDA receptor antagonists.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "NMDA receptor antagonists"
1
Madden, Ken. "NMDA Receptor Antagonists and Glycine Site NMDA Antagonists." Current Medical Research and Opinion 18, sup2 (January 2002): s27—s31. http://dx.doi.org/10.1185/030079902125000705.
Full text
2
Pedder, Simon C. J., Robert I. Wilcox, John M. Tuchek, Dennis D. Johnson, and R. D. Crawford. "Attenuation of febrile seizures in epileptic chicks by N-methyl-D-aspartate receptor antagonists." Canadian Journal of Physiology and Pharmacology 68, no. 1 (January 1, 1990): 84–88. http://dx.doi.org/10.1139/y90-012.
Full textAbstract:
Experimental febrile seizures can be evoked in epileptic chicks by elevation of their body temperature. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists [(3-(±)2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), DL-2-amino-7-phosphosphonoheptanoic acid (APH), DL-2-amino-5-phosphonovaleric acid (APV), D-α-aminoadipic acid (AAA), and DL-α,ε-diaminopimelic acid (DAP)] and the noncompetitive NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801) produced dose-dependent increases in latency to the onset of seizures. Of the drugs tested, MK-801 had the highest potency followed in order by CPP = APH > APV [Formula: see text] AAA > DAP. There was a high correlation (r = 0.995) between the dose capable of doubling seizure latency and the affinity of the competitive NMDA antagonists for the NMDA receptor as determined by in vitro binding assays. These data suggest that NMDA receptor mediated mechanisms may be involved in the production of seizures in response to hyperthermia.Key words: seizures, NMDA antagonists, epileptic chickens, anticonvulsant activity, receptors.
3
Heggelund, P., and E. Hartveit. "Neurotransmitter receptors mediating excitatory input to cells in the cat lateral geniculate nucleus. I. Lagged cells." Journal of Neurophysiology 63, no. 6 (June 1, 1990): 1347–60. http://dx.doi.org/10.1152/jn.1990.63.6.1347.
Full textAbstract:
1. Synaptic mechanisms that might explain the functional properties of the recently discovered class of lagged cells in the dorsal lateral geniculate nucleus (LGN) were analyzed with electrophysiological and pharmacologic techniques. To study the type of excitatory amino acid (EAA) receptor that mediates visual responses of lagged cells, we recorded the response of single cells to a stationary flashing light spot before, during, and after microiontophoretic application of antagonists and agonists to EAA receptors. 2. The visual response of the lagged cells could be almost completely blocked by an antagonist to the N-methyl-D-aspartate (NMDA) receptor. The degree of suppression was dose dependent, and the average maximum degree of suppression for all the cells was 94%. NMDA enhanced the response, and this enhancement was antagonized by NMDA antagonists. A quisqualate/kainate receptor antagonist had no significant effect on the lagged cells. 3. These findings indicate that the visual response in lagged cells is dependent upon activation of NMDA receptors, which may directly result from activation of retinal inputs. 4. No pharmacologic difference was seen between lagged X- and Y-cells, or between lagged ON- and OFF-center cells. 5. gamma-Aminobutyric acid-A (GABA-A) receptor antagonists were used to study whether the characteristic lag of the visual response and the suppression of the initial transient response component of the lagged cells are dependent on geniculate inhibition. Beside enhancement of the visual response, the GABA antagonists strongly reduced the lag of the visual response, and an initial transient response component occurred instead of the initial suppression. The lag remained slightly longer than for nonlagged cells, and the peak firing rate of the transient was below values typical for nonlagged cells, indicating that the lagged cell properties are dependent on other factors beside GABA-A receptor-mediated inhibition. 6. The enhanced visual response during iontophoresis of GABA antagonists could be completely blocked by simultaneous iontophoresis of an NMDA-receptor antagonist. This gives further support to the hypothesis that the retinal input to these cells is mediated by NMDA receptors. 7. The NMDA-receptor/ionophore complex mediates excitatory postsynaptic potentials (EPSPs) characterized by slow rise and decay times and long duration. The ionophore is characterized by a voltage-dependent blockade that makes these receptors particularly sensitive to inhibitory input. The temporal interplay between the slow NMDA receptor-mediated EPSPs and the fast GABA receptor-mediated inhibitory postsynaptic potentials (IPSPs) may explain the characteristic response properties of the lagged cells.
4
Grover, Lawrence M., and Chen Yan. "Evidence for Involvement of Group II/III Metabotropic Glutamate Receptors in NMDA Receptor–Independent Long-Term Potentiation in Area CA1 of Rat Hippocampus." Journal of Neurophysiology 82, no. 6 (December 1, 1999): 2956–69. http://dx.doi.org/10.1152/jn.1999.82.6.2956.
Full textAbstract:
Previous studies implicated metabotropic glutamate receptors (mGluRs) in N-methyl-d-aspartate (NMDA) receptor–independent long-term potentiation (LTP) in area CA1 of the rat hippocampus. To learn more about the specific roles played by mGluRs in NMDA receptor–independent LTP, we used whole cell recordings to load individual CA1 pyramidal neurons with a G-protein inhibitor [guanosine-5′-O-(2-thiodiphosphate), GDPβS]. Although loading postsynaptic CA1 pyramidal neurons with GDPβS significantly reduced G-protein dependent postsynaptic potentials, GDPβS failed to prevent NMDA receptor– independent LTP, suggesting that postsynaptic G-protein–dependent mGluRs are not required. We also performed a series of extracellular field potential experiments in which we applied group-selective mGluR antagonists. We had previously determined that paired-pulse facilitation (PPF) was decreased during the first 30–45 min of NMDA receptor–independent LTP. To determine if mGluRs might be involved in these PPF changes, we used a twin-pulse stimulation protocol to measure PPF in field potential experiments. NMDA receptor–independent LTP was prevented by a group II mGluR antagonist [(2S)-α-ethylglutamic acid] and a group III mGluR antagonist [(RS)-α-cyclopropyl-4-phosphonophenylglycine], but was not prevented by other group II and III mGluR antagonists [(RS)-α-methylserine-O-phosphate monophenyl ester or (RS)-α-methylserine-O-phosphate]. NMDA receptor–independent LTP was not prevented by either of the group I mGluR antagonists we examined, (RS)-1-aminoindan-1,5-dicarboxylic acid and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester. The PPF changes which accompany NMDA receptor–independent LTP were not prevented by any of the group-selective mGluR antagonists we examined, even when the LTP itself was blocked. Finally, we found that tetanic stimulation in the presence of group III mGluR antagonists lead to nonspecific potentiation in control (nontetanized) input pathways. Taken together, our results argue against the involvement of postsynaptic group I mGluRs in NMDA receptor–independent LTP. Group II and/or group III mGluRs are required, but the specific details of the roles played by these mGluRs in NMDA receptor–independent LTP are uncertain. Based on the pattern of results we obtained, we suggest that group II mGluRs are required for induction of NMDA receptor–independent LTP, and that group III mGluRs are involved in determining the input specificity of NMDA receptor–independent LTP by suppressing potentiation of nearby, nontetanized synapses.
5
Hanada, Takahisa. "Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors." Biomolecules 10, no. 3 (March 18, 2020): 464. http://dx.doi.org/10.3390/biom10030464.
Full textAbstract:
It is widely accepted that glutamate-mediated neuronal hyperexcitation plays a causative role in eliciting seizures. Among glutamate receptors, the roles of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in physiological and pathological conditions represent major clinical research targets. It is well known that agonists of NMDA or AMPA receptors can elicit seizures in animal or human subjects, while antagonists have been shown to inhibit seizures in animal models, suggesting a potential role for NMDA and AMPA receptor antagonists in anti-seizure drug development. Several such drugs have been evaluated in clinical studies; however, the majority, mainly NMDA-receptor antagonists, failed to demonstrate adequate efficacy and safety for therapeutic use, and only an AMPA-receptor antagonist, perampanel, has been approved for the treatment of some forms of epilepsy. These results suggest that a misunderstanding of the role of each glutamate receptor in the ictogenic process may underlie the failure of these drugs to demonstrate clinical efficacy and safety. Accumulating knowledge of both NMDA and AMPA receptors, including pathological gene mutations, roles in autoimmune epilepsy, and evidence from drug-discovery research and pharmacological studies, may provide valuable information enabling the roles of both receptors in ictogenesis to be reconsidered. This review aimed to integrate information from several studies in order to further elucidate the specific roles of NMDA and AMPA receptors in epilepsy.
6
Hartveit, E., and P. Heggelund. "Neurotransmitter receptors mediating excitatory input to cells in the cat lateral geniculate nucleus. II. Nonlagged cells." Journal of Neurophysiology 63, no. 6 (June 1, 1990): 1361–72. http://dx.doi.org/10.1152/jn.1990.63.6.1361.
Full textAbstract:
1. We studied the type of receptor for excitatory amino acids (EAA) that mediates visual responses of nonlagged cells in the dorsal lateral geniculate nucleus (LGN) by recording the visual response of single cells to a stationary flashing spot before, during, and after iontophoretical application of antagonists and agonists to EAA receptors. 2. The visual response of the nonlagged cells was strongly suppressed, in a dose-dependent manner, by the specific quisqualate/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). The average degree of suppression was 74%. Quisqualate enhanced the visual response. 3. Specific antagonists to the N-methyl-D-aspartate (NMDA) receptor had a weak suppressing effect on most nonlagged cells. The average degree of suppression was 22%. Measurement of such weak effects was complicated by the considerable spontaneous fluctuations of responsivity in the LGN cells. In the majority of cells where the visual response was suppressed by NMDA antagonists, the tonic response component was more strongly suppressed than the initial transient response component. The visual response was enhanced by NMDA, and this enhancement was antagonized by NMDA antagonists. 4. These findings suggest that the excitatory input from the retina to nonlagged LGN cells is mainly mediated by non-NMDA receptors. The non-NMDA receptors mediate fast EPSPs, and this can explain the fast onset and offset of the visual response of the nonlagged cells. 5. The generally small contribution from NMDA receptors to the visual response of the nonlagged cells might reflect a minor involvement of these receptors in the retinal input, or it could be related to the excitatory input to LGN from the visual cortex. 6. To study whether the expression of NMDA receptors was related to modulatory brain stem input to LGN, we examined the effects of the NMDA antagonists when the visual response was enhanced with gamma-aminobutyric acid (GABA) antagonists or acetylcholine (ACh). Neither of these pharmacologic manipulations consistently increased the relative contribution of NMDA receptors to the visual response. 7. No pharmacologic difference was found between nonlagged X- and Y-cells, or between ON- and OFF-center cells.(ABSTRACT TRUNCATED AT 400 WORDS)
7
Yuzaki, Michisuke, and John A. Connor. "Characterization of l-Homocysteate–Induced Currents in Purkinje Cells From Wild-Type and NMDA Receptor Knockout Mice." Journal of Neurophysiology 82, no. 5 (November 1, 1999): 2820–26. http://dx.doi.org/10.1152/jn.1999.82.5.2820.
Full textAbstract:
l-Homocysteic acid (HCA), an endogenous excitatory amino acid in the mammalian CNS, potently activates N-methyl-d-aspartate (NMDA) receptors in hippocampal neurons. However, the responses to HCA in Purkinje cells, which lack functional NMDA receptors, have been largely unexplored: HCA may activate conventional non-NMDA receptors by its mixed agonistic action on both NMDA and non-NMDA receptors, or it may activate a novel non-NMDA receptor that has high affinity for HCA. To test these possibilities, we compared the responses to HCA in cultured Purkinje cells with those in hippocampal neurons by using the whole cell patch-clamp technique. To clearly isolate HCA responses mediated by non-NMDA receptors, we complemented pharmacological methods by using neurons from mutant mice (NR−/−) that lack functional NMDA receptors. A moderate dose of HCA (100 μM) induced substantial responses in Purkinje cells. These responses were blocked by non-NMDA receptor antagonists but were insensitive to NMDA receptor antagonists. HCA also activated responses mediated by non-NMDA receptors in both wild-type and NR1−/− hippocampal neurons. HCA responses in Purkinje cells had a pharmacological profile (EC50 and Hill coefficient) very similar to that of non-NMDA receptor components of HCA responses in hippocampal neurons. Moreover, the amplitude of the non-NMDA receptor component of HCA responses was directly correlated with that of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)– and kainate-induced responses in both types of neurons. Finally, in both types of neurons, HCA currents mediated by non-NMDA receptors were potently blocked by the AMPA receptor antagonist GYKI52466. These findings indicate that HCA-activated AMPA receptors in Purkinje cells are similar to those in hippocampal neurons and that there is no distinct HCA-preferring receptor in Purkinje cells. We also found that in hippocampal neurons, the EC50s of HCA for non-NMDA receptors and for NMDA receptors were more similar than originally reported; this finding indicates that HCA is similar to other mixed agonists, such as glutamate. HCA responses may appear to be selective at NMDA receptors in cells that express these receptors, such as hippocampal neurons; in cells that express few functional NMDA receptors, such as Purkinje cells, HCA may appear to be selective at non-NMDA receptors.
8
Homayoun, Houman, Mark E. Jackson, and Bita Moghaddam. "Activation of Metabotropic Glutamate 2/3 Receptors Reverses the Effects of NMDA Receptor Hypofunction on Prefrontal Cortex Unit Activity in Awake Rats." Journal of Neurophysiology 93, no. 4 (April 2005): 1989–2001. http://dx.doi.org/10.1152/jn.00875.2004.
Full textAbstract:
Systemic exposure to N-methyl-d-aspartate (NMDA) receptor antagonists can lead to psychosis and prefrontal cortex (PFC)–dependent behavioral impairments. Agonists of metabotropic glutamate 2/3 (mGlu2/3) receptors ameliorate the adverse behavioral effects of NMDA antagonists in humans and laboratory animals, and are being considered as a novel treatment for some symptoms of schizophrenia. Despite the compelling behavioral data, the cellular mechanisms by which potentiation of mGlu2/3 receptor function attenuates the effects of NMDA receptor hypofunction remain unclear. In freely moving rats, we recorded the response of medial PFC (prelimbic) single units to treatment with the NMDA antagonist MK801 and assessed the dose-dependent effects of pre- or posttreatment with the mGlu2/3 receptor agonist LY354740 on this response. NMDA receptor antagonist-induced behavioral stereotypy was measured during recording because it may relate to the psychotomimetic properties of this treatment and is dependent on the functional integrity of the PFC. In most PFC neurons, systemic administration of MK801 increased the spontaneous firing rate, decreased the variability of spike trains, and disrupted patterns of spontaneous bursts. Given alone, LY354740 (1, 3, and 10 mg/kg) decreased spontaneous activity of PFC neurons at the highest dose. Pre- or posttreatment with LY354740 blocked MK801-induced changes on firing rate, burst activity, and variability of spike activity. These physiological changes coincided with a reduction in MK801-induced behavioral stereotypy by LY354740. These data indicate that activation of mGlu2/3 receptors reduces the disruptive effects of NMDA receptor hypofunction on the spontaneous spike activity and bursting of PFC neurons. This mechanism may provide a physiological basis for reversal of NMDA antagonist-induced behaviors by mGlu2/3 agonists.
9
Bryant, Camron D., Shoshana Eitan, Kevin Sinchak, Michael S. Fanselow, and Christopher J. Evans. "NMDA receptor antagonism disrupts the development of morphine analgesic tolerance in male, but not female C57BL/6J mice." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 291, no. 2 (August 2006): R315—R326. http://dx.doi.org/10.1152/ajpregu.00831.2005.
Full textAbstract:
Multiple studies demonstrate that coadministration of N-methyl-d-aspartate (NMDA) receptor antagonists with the opioid agonist morphine attenuates the development of analgesic tolerance. Sex differences in the effects of noncompetitive, but not competitive NMDA receptor antagonists on acute morphine analgesia, have been reported in mice, yet the role of sex in modulation of morphine tolerance by NMDA receptor antagonists has yet to be addressed. Therefore, we tested whether there is a sex difference in the effect of NMDA receptor antagonists on the development of morphine analgesic tolerance in C57BL/6J mice. Acutely, at a dose required to affect morphine tolerance in male mice, the noncompetitive NMDA receptor antagonist dizocilpine (MK-801) prolonged morphine analgesia similarly in both sexes in the hot plate and tail withdrawal assays. In the hot plate assay, coadministration of MK-801 or the competitive antagonist 3-(2-carboxpiperazin-4-yl)propyl-1-phosphanoic acid (CPP) with morphine attenuated the development of tolerance in male mice, while having no effect in females. Like normal and sham females, ovariectomized mice were similarly insensitive to the attenuation of morphine tolerance by MK-801 in the hot plate assay. Surprisingly, in the tail withdrawal assay, MK-801 facilitated the development of morphine-induced hyperalgesia and tolerance in males but not females. The results demonstrate that male mice are more sensitive to modulation of nociception and morphine analgesia after repeated coadministration of NMDA receptor antagonists. Furthermore, the underlying mechanisms are likely to be different from those mediating the sex difference in the modulation of acute morphine analgesia that has previously been reported.
10
Butcher, Kenneth S., and David F. Cechetto. "Receptors in lateral hypothalamic area involved in insular cortex sympathetic responses." American Journal of Physiology-Heart and Circulatory Physiology 275, no. 2 (August 1, 1998): H689—H696. http://dx.doi.org/10.1152/ajpheart.1998.275.2.h689.
Full textAbstract:
Previous evidence has shown that sympathetic nerve responses to insular cortical (IC) stimulation are mediated by synapses within the lateral hypothalamic area (LHA) and ventrolateral medulla. The present study determined the receptor(s) involved at the synapse in the LHA associated with stimulation-evoked IC sympathetic responses. Twenty-seven male Wistar rats were instrumented for renal nerve activity, arterial pressure, and heart rate recording. The right IC was stimulated with a bipolar electrode (200–1,000 μA, 2 ms, 0.8 Hz) resulting in sympathetic nerve responses. Antagonists were then pressure injected into the ipsilateral LHA (300–500 nl). Kynurenate (250 mM) injections resulted in 51 ± 8% (range 0–100%) block of IC-stimulated sympathetic nerve responses. Similarly, the N-methyl-d-aspartic acid (NMDA)-receptor antagonistdl-2-amino-5-phosphonopentanoic acid (200 μM) resulted in an inhibition (82 ± 8%; range 51–100%) of IC-stimulated sympathetic responses. Injection of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (200 μM) had no effect on IC sympathetic responses. Injection of antagonists to GABA, acetylcholine, and adrenergic receptors was also without effect. No antagonist injections had any effects on baseline sympathetic nerve discharge, arterial pressure, or heart rate. These results suggest that the IC autonomic efferents projecting to the LHA utilize NMDA glutamatergic receptors.
Dissertations / Theses on the topic "NMDA receptor antagonists"
1
Gutnikov, Sergei A. "Behavioural studies of the NMDA system in rats." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294382.
Full text
2
Wilson, John A. "The role of N-methyl D-aspartate (NMDA) receptor antagonists in neuropathic pain." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/25324.
Full textAbstract:
The aim of this thesis is to investigate the use of NMDAR antagonists in preventing naturopathic sensitisation. The chronic constriction injury (CCI) model of neuropathic pain is used to study the role of NMDARs in the development of neuropathic pain and subsequent modulation. Behavioural effects are assessed in association with changes in NMDAR subtypes. Memantine and ketamine (NMDAR antagonists) are shown to attenuate typical behavioural responses (thermal hyperalgesia and cold allodynia) to nerve injury. In addition, NMDAR antagonist pre-treatment is shown to effect the subsequent NMDAR subunit expression, with improved susceptibility to subsequent NMDAR antagonist treatment. The clinical use of epidural ketamine as a preventative drug prior to lower limb amputation is investigated in a double blind randomised placebo controlled study. No significant effects on the incidence of post-amputation pain were found, although the overall incidence of pain was lower than in comparable studies. Ketamine is shown to improve peri-operative analgesia and have long lasting effects (up to one week) on sensory processing in the remaining stump. In summary, NMDAR antagonists seem to be effective in attenuating neuropathic pain in animal models. The promise shown in these studies has not translated into a reduction in post-amputation pain in a clinical study. Ketamine remains a clinically useful drug in peri-operative pain management but the role of ketamine and other clinically available NMDAR antagonists in the prevention of neutropathic sensitisation is still not clearly defined.
3
Dutta, Arpan. "The effect of NMDA receptor antagonists and antidepressants on resting state in major depressive disorder." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/the-effect-of-nmda-receptor-antagonists-and-antidepressants-on-resting-state-in-major-depressive-disorder(0c1dd1fc-ff39-43fb-92c0-7b108e4f6230).html.
Full textAbstract:
Introduction: The aim of the project was to investigate the effects of antidepressants on brain networks whilst at rest. My hypothesis was that antidepressants work by reversing persistent activity in the brain’s default mode network (DMN). The DMN is implicated in self-reflection and rumination in MDD. The methodologies and results of studies of resting state networks in MDD and the effects of antidepressants are reviewed in the thesis. Increasing evidence implicates glutamate in the action of antidepressant drugs. Whether there are illness related changes in glutamate function is unresolved, largely because of the lack of techniques for assessing it. Ketamine and other NMDA antagonists have improved MDD symptoms within 24 hours though the effects are short lasting. The molecular neural networks involved in ketamine’s putative antidepressant effects are unclear. The thesis reviews the evidence. Much evidence implicates ACC as a site of action of antidepressant effects but whether this is through its regulation of the DMN or other networks is not known. This thesis compares the effect of ketamine and citalopram on ACC-related systems. Method: The thesis combines two systematic reviews of the effects of MDD and antidepressant drugs on i) resting state networks (53 studies) and ii) glutamate neurotransmission (45 studies of clinical efficacy of ketamine). There are two experimental chapters. The first describes investigation into two rapid acting antidepressant drugs acting via glutamate mechanisms. 54 unmedicated cMDD were scanned across two centres on 3T MRI scanners while being infused with placebo (0.5% saline), 0.5mg/kg ketamine or 100mg AZD6765 over 1 hour. fMRI resting state data between drug treatments was compared for the final 25 minutes of the drug infusion and for a 25 minute resting state scan a day later. The second experimental chapter examines whether these effects were shared by citalopram, a standard antidepressant. 67 unmedicated cMDD, rMDD and HC were administered citalopram 7.5mg i.v. and scanned on a 1.5T MRI scanner. In a second study 63 cMDD and HC were administered i.v. citalopram 7.5mg or placebo (0.5% saline). fMRI resting state data for the final 12 ½ minutes following drug infusion was compared. Independent Component Analysis was performed using the Group ICA for fMRI toolbox. The resting component with the highest spatial correlation to the ACC was used. Brain maps of the intensity of the selected component were constructed for each individual. Group averages were calculated and compared using SPM. Regional analysis was performed using Marseille Boite a Regions d'interet. Results: On day 1 AZD6765 significantly increased mean intensity of ACC resting component in the right insula, right IPL and left cingulate gyrus greater than ketamine or placebo. Ketamine increased mean intensity of ACC resting component greater than placebo in the right lentiform nucleus and left mFG. Significantly decreased mean intensity of ACC resting component in the left insula in the AZD6765 group compared to placebo was noted. On day 2 AZD6765 increased mean intensity of ACC resting component greater than ketamine and placebo in the left and right lentiform nuclei. AZD6765 reduced mean intensity of the ACC resting component in the left and right MFG. The first citalopram study revealed reduced mean intensity of ACC resting component in cMDD compared to rMDD and HC in PCC. rMDD had reduced mean intensity of ACC resting component in the precuneus compared to HC. In the second study, citalopram had no effect in HC but normalised precuneus activity in cMDD producing a significant drug x group interaction. Conclusions: The acute antidepressant effects of citalopram are modulated by changes in the bilateral precuneus. The precuneus is central to connectivity with other regions in MDD. It has a prominent role in the DMN and is linked to rumination. The mechanism of the antidepressant effects of AZD6765 is different from those of ketamine and citalopram. The insula, IPL, MFG, cingulate gyrus and lentiform nuclei are all regions implicated in MDD suggesting antidepressant effects. The rapid antidepressant effects of AZD6765 are possibly due to a resetting of the interface between DMN and salience networks.
4
Brazaitis, Casmira T. "In vivo and in vitro studies of positive allosteric modulation of the NMDA receptor." Thesis, University of St Andrews, 2017. http://hdl.handle.net/10023/10495.
Full textAbstract:
Dysfunction of the N-methyl-D-aspartate (NMDA) receptor is thought to contribute to the cognitive deficits of many neurodegenerative diseases and psychiatric disorders. Cognitive symptoms of Alzheimer's disease can be treated with NMDA receptor antagonists or drugs targeting the cholinergic system; however, there are no effective treatments for cognitive deficits of schizophrenia or Huntington's disease. With the discovery of a potent and selective allosteric modulator of the NMDA receptor, there is the possibility of new treatments based on NMDA receptor functional-enhancement through neuroactive steroids, closely related in structure to the endogenous neurosteroid, cerebrosterol. The aim of this thesis was to examine steroidal modulation of the NMDA receptor both in vitro and in vivo. In chapter 2, NMDA receptor enhancement of both the synthetic and endogenous neuroactive steroids was assessed in neurons maintained in cell culture using calcium imaging techniques. Sulphation of the steroids greatly increased the efficacy of NMDA receptor enhancement compared to the unsulphated steroids. Chapters 3 and 4 investigate the potential for neuroactive steroids to treat cognitive impairments of Huntington's disease. Using a mouse model, tests were selected that were analogous to those in which patients are impaired; however, no impairments were found in the mouse model. Chapter 5, therefore, used a different model of cognitive impairment – namely, rats with a set-shifting impairment, as is seen in many psychiatric and neurological disorders, including Huntington's disease – to assess the effect of the synthetic steroid administration. Unfortunately, the rats did not show the expected impairment. The lack of reliable animal models compromised testing the efficacy of these promising NMDA receptor positive allosteric modulators. Nevertheless, the promising in vitro results suggest that there could still be therapeutic potential. In addition, the compound is a useful research tool for exploring NMDA receptor function in health and disease.
5
Tarrés, Gatius Mireia. "Neurobiological mechanisms involved in the antidepressant and psychotomimetic effects of NMDA receptor antagonists: role of the GluN2C subunit." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/669917.
Full textAbstract:
Sub-anesthetic doses of ketamine evoke rapid and persistent antidepressant effects in treatment-resistant depressed patients through still poorly-known mechanisms. Ketamine also evokes transient psychotomimetic effects, shared by other non-competitive NMDA-R antagonists such as phencyclidine (PCP) and dizocilpine (MK-801), which are used as pharmacological models of schizophrenia. Previous studies indicate that PCP activates thalamo- cortical circuits after the blockade of NMDA-R in GABAergic neurons of the reticular nucleus (RtN). Given that one of the sites of action of non-competitive NMDA-R antagonists is the RtN and that the GluN2C subunit is expressed in this nucleus, our working hypothesis was that the psychotomimetic and the antidepressant-like effects induced by non-competitive NMDA-R antagonists would be partly attenuated in absence of the GluN2C subunit.
All three NMDA-R antagonists induced psychotomimetic effects in both genotypes. While locomotor activity was increased in GluN2CKO mice, stereotyped behaviors like circling and ataxia signs (falls, hindlimb abduction) were dramatically attenuated, suggesting a better motor coordination in absence of the GluN2C subunit. In agreement, GluN2CKO mice spent more time on the rotarod compared to WT mice after PCP or MK-801 administration. However, there were no genotype differences in the PPI test, showing that the GluN2C subunit is not involved in sensory gating. Moreover, PCP and MK-801 evoked a general pattern of c-fos activation, except in cerebellum, where significant reductions and genotype differences were noted. Ketamine reduced the immobility time in male and female WT and GluN2CKO mice in tests used for the screening of antidepressants, showing that the GluN2C subunit does not contribute to the antidepressant-like effects induced by ketamine in both sexes. This acute antidepressant-like effect might be mediated by a transient increase of serotonin, but not glutamate, in the medial prefrontal cortex. Moreover, ketamine increased c-fos expression in the thalamus of female but not male mice, while reductions were only present in the cerebellum of male mice, suggesting sex-differentiated effects of ketamine. Regarding NMDA-R subunits distribution, deletion of the GluN2C subunit led to minor changes in the expression of GluN2A, GluN2B or GluN2D subunits, suggesting that it was not systematically replaced by any other GluN2 subunits. However, it produced remarkable changes in the expression of the GluN1 subunit in cerebellar and thalamic areas, which may contribute to the behavioral and molecular differences between both genotypes.
In conclusion, the GluN2C subunit appears to be strongly involved in motor components of the behavioral syndrome induced by non-competitive NMDA-R antagonists, while the antidepressant-like effects of ketamine are preserved. Its genetic deletion results in an improved motor coordination after NMDA-R blockade. This supports the presence of GluN2C‐containing NMDA‐R in cerebellar circuits controlling motor activity and equilibrium, which are sensitive to the action of ketamine, PCP, and MK-801. Overall, the present study supports the involvement of cerebellar GluN2C subunits as a key element in the psychotomimetic actions of non- competitive NMDA-R antagonists. The differential role of the GluN2C subunit in mediating the psychotomimetic and antidepressant effects of ketamine identifies this subunit as a potential target for preventing the emergence of pro-psychotic effects while keeping a full antidepressant action.La ketamina, la fenciclidina (PCP) y la dizocilpina (MK-801) son antagonistas no competitivos del receptor NMDA y se utilizan como modelos farmacológicos de esquizofrenia ya que su administración evoca unos síntomas parecidos a los de un estado psicótico. Además, la ketamina también ejerce un efecto antidepresivo rápido y sostenido en el tiempo en pacientes depresivos resistentes a los tratamientos convencionales. Estudios previos han demostrado que PCP actuaría preferencialmente sobre neuronas GABAérgicas del núcleo reticular del tálamo, bloqueando su efecto inhibidor y, en consecuencia, activando circuitos tálamo-corticales. Dado que la subunidad GluN2C del NMDA-R se expresa en dicho núcleo talámico, en esta tesis hemos estudiado la posible implicación de la subunidad GluN2C en los efectos psicotomiméticos y antidepresivos inducidos por los antagonistas no competitivos del NMDA-R, bajo la hipótesis de trabajo de que estos efectos serían menores en ausencia de dicha subunidad. El tratamiento agudo con MK-801, PCP y ketamina indujo efectos psicotomiméticos en ratones WT y GluN2CKO. No obstante, la intensidad de las rotaciones (movimiento estereotipado), el número de caídas y el arrastrado de patas traseras (signos de ataxia) fueron significativamente menores en los ratones GluN2CKO, sugiriendo una mejor coordinación motora en ausencia de la subunidad GluN2C. De acuerdo con estos resultados, en los ratones GluN2CKO observamos un mayor tiempo de permanencia en el rotarod en comparación con los ratones WT tras la administración aguda de MK-801 o PCP. Sin embargo, no encontramos diferencias de genotipo en el test de la inhibición pre-pulso, sugiriendo que la subunidad GluN2C no estaría relacionada con la regulación sensoriomotora. La administración de MK-801 y PCP provocó un aumento generalizado de la expresión del gen c-fos en el cerebro de los ratones WT y GluN2CKO, excepto en el cerebelo, dónde se observaron reducciones y diferencias de genotipo en su expresión. Respecto a los efectos antidepresivos, ketamina redujo el tiempo de inmovilidad en machos y hembras WT y GluN2CKO, sugiriendo que la subunidad GluN2C no está involucrada en la acción antidepresiva de ketamina. Además, ketamina aumentó la liberación de serotonina en la corteza prefrontal en ambos géneros, sugiriendo que el efecto antidepresivo podría estar relacionado con este neurotransmisor. En comparación con MK-801 y PCP, el patrón de expresión de c-fos después de la administración de ketamina no fue tan intenso y se observaron diferencias de género. En conclusión, este trabajo demuestra que existe una disociación en cuanto a la participación de la subunidad GluN2C en los efectos motores y el efecto antidepresivo inducidos por antagonistas no competitivos del NMDA-R. Debido a que la subunidad GluN2C se encuentra altamente expresada en el cerebelo y que ésta es un área involucrada en coordinación motora, los NMDA-R de cerebelo podrían jugar un papel importante en el mecanismo de acción de MK-801, PCP y ketamina.
6
Mathé, Jan M. "The phencyclidine model of schizophrenia : dysregulation of brain dopamine systems induced by NMDA receptor antagonists : an experimental study /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980930math.
Full text
7
Hillhouse, Todd. "Dissociable antidepressant-like and abuse-related effects of the noncompetitive NMDA receptor antagonists ketamine and MK-801 in rats." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3326.
Full textAbstract:
The noncompetitive NMDA receptor antagonist ketamine produces rapid and sustained antidepressant effects in patients suffering from major depressive disorder. However, abuse liability is a concern. To further evaluate the relationship between antidepressant-like and abuse-related effects of NMDA receptor antagonists, this study evaluated the effects of ketamine, MK-801, and phencyclidine in male Sprague-Dawley rats responding under two procedures that have been used to assess antidepressant-like effects [differential-reinforcement-of-low-rate (DRL) 72 s schedule of food reinforcement] and abuse-related drug effects [intracranial self-stimulation (ICSS)]. Under DRL 72 s, ketamine produced an antidepressant-like effect by increasing reinforcers, decreasing responses, and producing a rightward shift in the peak location of the interresponse time (IRT) distributions. Phencyclidine produced a modest antidepressant-like effect by increasing reinforcers and decreasing responses, but did not shift the IRT distributions. In contrast, MK-801 produced a psychostimulant-like effect by decreasing reinforcers, increasing responses, and producing a leftward shift in the peak location of the IRT distributions. The antidepressant-like effects of ketamine on the DRL 72 s procedure do not appear to be mediated by inhibiting the reuptake of serotonin via serotonin transporters or antagonism of 5-HT2 receptors. Additionally, the dissociable effects of ketamine and MK-801 in the DRL 72 s procedure may be mediated by 5-HT2 receptors. Following acute administration, ketamine produced only dose- and time-dependent depression of ICSS and failed to produce an abuse-related facilitation of ICSS at any dose or pretreatment time. Repeated dosing with ketamine produced dose-dependent tolerance to the rate-decreasing effects of ketamine but failed to unmask expression of ICSS facilitation. Termination of ketamine treatment failed to produce withdrawal-associated decreases in ICSS. In contrast, MK-801 and phencyclidine effects produced dose- and time-dependent facilitation of ICSS by MK-801. Taken together, our findings provide further evidence that expression of these antidepressant-like and abuse-related effects of ketamine, phencyclidine, and MK-801 may be related to NMDA receptor affinity.
8
Wang, Yachao [Verfasser], and Dirk [Akademischer Betreuer] Hermann. "Post-acute delivery of NMDA or GABAA α5 receptor antagonists promotes neurological recovery and peri-infarct brain remodeling after transient focal cerebral ischemia in mice / Yachao Wang ; Betreuer: Dirk Hermann." Duisburg, 2019. http://d-nb.info/1191692272/34.
Full text
9
Berry, Jennifer N. "THE MESOCORTICOLIMBIC DOPAMINE PATHWAY RECONSTITUTED IN VITRO: GLUTAMATE RECEPTORS AND CORTICOSTEROID-METHAMPHETAMINE NEUROTOXICITY." UKnowledge, 2013. http://uknowledge.uky.edu/psychology_etds/28.
Full textAbstract:
Stress promotes the use of methamphetamine and other recreational substances and is often implicated in relapse to stimulant use. Thus, it is of critical importance to examine the consequences of the co-occurance of stress and methamphetamine use. Activity of the glutamatergic N-methyl D-aspartate (NMDA) receptor system appears to be involved in the neurotoxic effects of both chronic stress and methamphetamine exposure. The current studies investigated the hypothesis that chronic pre-exposure to the stress hormone corticosterone (CORT) results in an increase of NMDA receptor activity and that this will potentiate the neurotoxic effects of methamphetamine (METH). Co-cultures of the ventral tegmental area, nucleus accumbens, and medial prefrontal cortex were pre-exposed to CORT (1 μM) for 5 days prior to co-exposure to METH (100 μM) for 24 hours to investigate the combined effects on neurotoxicity and protein density of NMDA receptor subunits. The combination of CORT and METH resulted in significant neurotoxicity within the medial prefrontal cortex compared to either CORT or METH alone. The CORT+METH-induced toxicity was attenuated by co-exposure to the NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV; 50 μM) during the 24 hour CORT and METH co-exposure. Although CORT alone did not significantly alter the density of the NR1 and NR2B subunits of the NMDA receptor, METH exposure for 24 hours resulted in a significant loss of the polyamine sensitive NR2B subunit. Co-exposure to CORT and METH also resulted in decreased extracellular glutamate while not significantly altering extracellular dopamine. These results suggest an enhancement of NMDA receptor systems or downstream effectors in areas of the mesolimbic reward pathway following chronic pre-exposure to CORT, which leads to enhanced neuronal vulnerability to future excitotoxic insults. This may be of critical importance as use of psychostimulants such as METH and other drugs of abuse may produce excitotoxic events in these areas, thus further compromising neuronal viability.
10
Deshpande, Laxmikant Sudhir. "Glutamate Excitotoxicty Activates a Novel Calcium Permeable Ion Channel in Cultured Hippocampal Neurons." VCU Scholars Compass, 2006. http://scholarscompass.vcu.edu/etd/688.
Full textAbstract:
Glutamate excitotoxicity is the predominant mechanism implicated in neuronal cell death associated with neurological disorders such as stroke, epilepsy, traumatic brain injury and ALS. Excessive stimulation of NMDA subtypes of glutamate receptors leads to protracted intracellular calcium elevations triggering calcium mediated neurotoxic mechanisms culminating in delayed neuronal cell death. In addition, glutamate excitotoxicity induces a NMDA dependent extended neuronal depolarization mediated by continuous calcium influx that correlates with delayed neuronal death. Attempts to prevent neuronal death by blocking calcium entry into the neurons using calcium channel blockers or NMDA receptor antagonists have failed to provide any beneficial effects in clinical trials. Thus, calcium continues to enter the neurons despite the presence of calcium entry blockers. This phenomenon is known as the "calcium paradox of stroke" and represents a major problem in developing effective therapies for treatment of stroke. Here employing a combination of patch clamp recordings, fluorescent calcium imaging and neuronal cell death assays in well-characterized in vivo and in vitro models of glutamate excitotoxicity, we report the discovery of a novel calcium permeable ion channel that is activated by excitotoxic glutamate injury and mediates a calcium current that is an early initiating step in causing neuronal death. Blocking this calcium permeable channel with high concentrations of Zn2+ or Gd3+ by removing extracellular calcium for a significant time period after the initial injury is effective in preventing calcium entry, apoptosis and neuronal death, thus accounting for the calcium paradox. This injury induced-calcium permeable channel provides a unique mechanism for calcium entry following stroke and offers a new target for extending the therapeutic window for preventing neuronal death after the initial excitotoxic (stroke) injury.
Books on the topic "NMDA receptor antagonists"
1
Feng, Alexander J., George C. Chang Chien, and Alan D. Kaye. NMDA Receptor Antagonists, Gabapentinoids, Alpha-2 Agonists, and Dexamethasone. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190457006.003.0002.
Full textAbstract:
Surgical pain is a major obstacle in the recovery of patients. Effective pain management is of upmost importance to optimize a patient’s recovery, decrease medical complications, and increase patient satisfaction. Traditional pain management with opioids and nonsteroidal anti-inflammatory drugs have significant side effect profiles leading to medical complications or insufficient pain management from reluctance of use. Adjuvant analgesic can provide improved pain management with significantly less side effect profile. In addition, the clinician can, with synergistic effects of adjuvant medications, lower the total dosages used, thus lessening the likelihood of the side effects that occur when medications are used alone at a higher dosage. This chapter presents several adjuvant analgesics—NMDA receptor antagonists, gabapentinoids, alpha-2 agonists, and dexamethasone—and evidence for their use. Ultimately, through the use of traditional pain management options along with adjuvant analgesics, the effectiveness of acute pain management can be increased while adverse outcomes are reduced and functional recovery and quality of life improved.
2
Farfel, Gail Meredith. Co-administration of NMDA receptor antagonists with neurotoxic amphetamine analogs: Protection against serotonergic toxicity mediated via hypothermia. 1993.
Find full text
3
Henter, Ioline D., and Rodrigo Machado-Vieira. Novel therapeutic targets for bipolar disorder. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198748625.003.0030.
Full textAbstract:
The long-term course of bipolar disorder (BD) comprises recurrent depressive episodes and persistent residual symptoms for which standard therapeutic options are scarce and often ineffective. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors have consistently been implicated in the pathophysiology of mood disorders and in the development of novel therapeutics for these disorders. Since the rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000, other NMDA receptor antagonists have been studied in major depressive disorder (MDD) and BD. This chapter reviews the clinical evidence supporting the use of novel glutamate receptor modulators for treating BD—particularly bipolar depression. We also discuss other promising, non-glutamatergic targets for potential rapid antidepressant effects in mood disorders, including the cholinergic system, the melatonergic system, the glucocorticoid system, the arachidonic acid (AA) cascade, and oxidative stress and bioenergetics.
4
Ren, Ke, and Ronald Dubner. The first crystal structure of an ionotropic glutamate receptor ligand-binding core. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0032.
Full textAbstract:
The known functional ionotropic glutamate receptors (iGluRs) are composed of three major subtypes: AMPA, NMDA, and kainate. In 1998, in the landmark paper discussed in this chapter, Armstrong et al. provided the first crystal structure of an iGluR-subunit ligand-binding core, the S1S2 region of the rat GluA2 ‘flop’ isoform. They solved its structure with X-ray crystallography from selenomethonine crystals. They also identified residues involved in kainate binding, analysed allosteric sites that regulate affinity and specificity of the agonist, and mapped potential subunit–subunit interaction sites. They also proposed that binding of different agonists may result in variable degrees of domain closure. This work has profound impact on the field and it has been importantly cited. Subsequently, numerous high-resolution crystal structures of ligand-binding domains of iGluRs in complex with ligands, both agonists and antagonists, have been solved.
5
Fomberstein, Kenneth, Michael Rubin, Dipan Patel, Ivona Truszkowska, and S. Gabriel Farkas. Perioperative Nonopioid Analgesics of Use in Pain Management for Spine Surgery. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190626761.003.0003.
Full textAbstract:
This chapter examines the developing role of multimodal analgesia in reducing opioid requirements/dependency in the postoperative period while also facilitating the recovery process without the unwanted adverse side effects associated with opioid use. It reviews a number of medications used in a multimodal regimen including NMDA receptor antagonists, α2 agonists, dexamethasone, gabapentinoids, acetaminophen, NSAIDs, COX-2 selective inhibitors, caffeine, and lidocaine. This chapter also discusses the evidence and implications for the use of a specific medication and in which perioperative setting its use has been corroborated. This chapter includes relevant tables and is written for qualified specialist attendings, fellows, residents, and nurses as well as all practitioners involved in the treatment of pain following spine surgery.
6
Dahl, Vegard, and Ulrich J. Spreng. Anaesthesia for non-obstetric surgery. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198713333.003.0010.
Full textAbstract:
Anaesthesia for non-obstetric reasons is performed in 1–2% of all pregnant women. Although the chances of complications like miscarriage, preterm labour, and abortion are higher when surgery is performed during gestation, careful evaluation, preparation, and a multidisciplinary approach will minimize these risks. There are no methods of anaesthesia that are preferable to others during pregnancy. The most important preventive measure is to maintain maternal haemodynamic stability and normoventilation in order to ensure fetal well-being. Extensive knowledge of the profound anatomical and physiological changes that a pregnancy induces is mandatory for the team when operating on a pregnant woman. Short time exposure to anaesthetic agents in clinically relevant doses during surgery has never been demonstrated to have teratogenic effects. Lately, focus has been made on the possible behavioural teratogenic properties of anaesthesia, especially on the use of NMDA receptor antagonists and GABA receptor agonists. Emergency diagnostic imaging during pregnancy is considered safe and should be performed if necessary. Electroconvulsive therapy for the treatment of serious psychiatric disorders during pregnancy is a possibility that should be considered if necessary. Electric cardioversion seems safe for the fetus if life-threatening arrhythmias occur during pregnancy. Trauma is one of the leading non-obstetric causes of maternal mortality and morbidity. When treating a traumatized pregnant woman one should initially focus on the mother’s safety and haemodynamic stability.
7
Dalip J.S. Sirinathsinghji (Editor) and Ray G. Hill (Editor), eds. NMDA antagonists as potential analgesic drugs (Progress in Inflammation Research). Birkhäuser Basel, 2002.
Find full text
8
Black, Sheila. The original description of central sensitization. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0040.
Full textAbstract:
The landmark study discussed in this chapter is ‘The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury’, published by Coderre and Melzack in 1992. Previous studies in this field implicate a contribution of excitatory amino acids (EAAs), specifically l-glutamate and l-aspartate, to injury-induced sensitization of nociceptive responses in the dorsal horn of the spinal cord. Repetitive stimulation of primary afferent fibres demonstrated that l-glutamate and NMDA can produce ‘wind-up’ of neuronal dorsal horn activity, and this is blocked by application of NMDA antagonists. This study uses the formalin test as a behavioural model to investigate the mechanisms underlying central sensitization and the role of EAAs, NMDA, their receptors, and their antagonists in this process.
9
Sano, Mary, and Judith Neugroschil. Current Treatments for Alzheimer’s Disease. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0057.
Full textAbstract:
Five medications representing two classes of drugs have been approved by the US Food and Drug Administration for the treatment of Alzheimer’s disease since 1994. There have been no new approved agents since 2003, although hundreds of clinical trials are in progress. This chapter reviews the pharmacology underlying the currently approved treatments, acetylcholinesterase inhibitors and the NMDA receptor antagonist memantine, and the data supporting their efficacy. Other approaches currently in use or being developed are also reviewed, including the use of hormones, agents that modify cardiovascular and metabolic risk, as well as a number of vitamin supplements and nutritional approaches.
10
Shapiro, Benjamin. Ibogaine: History, Pharmacology, Spirituality, & Clinical Data. Edited by Shahla J. Modir and George E. Muñoz. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190275334.003.0027.
Full textAbstract:
Ibogaine is an indole alkaloid derived from the African shrub Tabernathe iboga with broad anti-addictive, anti-depressant, and central nervous system stimulating effects. It is categorized as an oneriogen (or atypical hallucinogen) and has been used in West African tribal rituals for centuries. It was identified by French explorers in the early 1900s, came to the United States in the 1960s, and became marginalized in the mid-1990s after adverse outcomes halted federally funded human trials. Since then legal ibogaine treatment clinics have been established in countries without use restrictions. Ibogaine is a σ1 and σ2 receptor and μ and κ opioid receptor agonist and a α3β4 nicotinic and NMDA receptor antagonist. Decades of trials have demonstrated ibogaine’s potential. Human trials of ibogaine consistently demonstrate rapid remission of acute withdrawal symptoms but differ in their findings with regard to abstinence and toxicity. While ibogaine is not a “magic bullet,” considerable abstinence may result after multiple treatments, however QT prolongation can produce lethal ventricular tachyarrhythmias.18 MC is in pre-clinical investigation.
Book chapters on the topic "NMDA receptor antagonists"
1
Schroeder, Carrie, and Kristopher Schroeder. "NMDA Receptor Antagonists." In Pain, 285–87. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-319-99124-5_62.
Full text
2
Kamdar, Mihir M. "Ketamine and NMDA-Receptor Antagonists." In Deer's Treatment of Pain, 199–204. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-12281-2_24.
Full text
3
Rajdev, Sunita, and Frank R. Sharp. "Neurotoxiciy of NMDA Receptor Antagonists." In Highly Selective Neurotoxins, 355–84. Totowa, NJ: Humana Press, 1998. http://dx.doi.org/10.1007/978-1-59259-477-1_14.
Full text
4
Ma, Qing-Ping, and Clifford J. Woolf. "The NMDA receptor, pain and central sensitization." In NMDA Antagonists as Potential Analgesic Drugs, 83–103. Basel: Birkhäuser Basel, 2002. http://dx.doi.org/10.1007/978-3-0348-8139-5_5.
Full text
5
Sang, Christine N. "Clinically available glutamate receptor antagonists in neuropathic pain states." In NMDA Antagonists as Potential Analgesic Drugs, 165–80. Basel: Birkhäuser Basel, 2002. http://dx.doi.org/10.1007/978-3-0348-8139-5_9.
Full text
6
Boyce, Susan G., and Nadia M. J. Rupniak. "Behavioural studies on the potential of NMDA receptor antagonists as analgesics." In NMDA Antagonists as Potential Analgesic Drugs, 147–64. Basel: Birkhäuser Basel, 2002. http://dx.doi.org/10.1007/978-3-0348-8139-5_8.
Full text
7
Dickenson, Anthony H., and Fiona C. Taylor. "Interaction of NMDA and other neurotransmitter receptor systems in modulation of nociception." In NMDA Antagonists as Potential Analgesic Drugs, 129–46. Basel: Birkhäuser Basel, 2002. http://dx.doi.org/10.1007/978-3-0348-8139-5_7.
Full text
8
Vorobeychik, Yakov, Channing D. Willoughby, and Jianren Mao. "NMDA Receptor Antagonists in the Treatment of Pain." In Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches, 61–67. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-1560-2_6.
Full text
9
Vorobeychik, Yakov, Channing D. Willoughby, and Jianren Mao. "NMDA Receptor Antagonists in the Treatment of Pain." In Treatment of Chronic Pain by Medical Approaches, 59–65. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1818-8_6.
Full text
10
Kemp, J. A., J. N. C. Kew, and R. Gill. "NMDA Receptor Antagonists and Their Potential as Neuroprotective Agents." In Ionotropic Glutamate Receptors in the CNS, 495–527. Berlin, Heidelberg: Springer Berlin Heidelberg, 1999. http://dx.doi.org/10.1007/978-3-662-08022-1_16.
Full textConference papers on the topic "NMDA receptor antagonists"
1
Gómez-Carreño, Carlos Rodríguez, Antonio Ramírez García, Luis Beato Fernández, Irene Díaz Quero, and Estefanía Segura Escobar. "Craving and Priming of alcohol in depressive disorders. Bibliographic review and new therapies." In 22° Congreso de la Sociedad Española de Patología Dual (SEPD) 2020. SEPD, 2020. http://dx.doi.org/10.17579/sepd2020p140.
Full textAbstract:
Acute alcohol consumption produces positive reinforcement effects, through activation of brain reward circuit, includes limbic system structures (accumbens system and hippocampus). The comorbidity of depressive episode and alcohol abuse makes it necessary to propose new strategies for the treatment of this frequent clinical situation. We conducted a literature review of the combined treatments for major depressive disorder (MDD) with alcohol abuse. We review current literature on the use of new treatments in alcohol consumption with pattern of abuse (binge drinking). Recent studies support the potential clinical importance of NMDA receptor antagonism among the mechanisms underlying the subjective effects of ethanol in humans. The efficacy of medications for alcohol dependence remains modest, and there are no strong clinical predictors of treatment response. We analyze approved medications used today: Acamprosate (NMDA modulator), disulfiram (acetaldehyde dehydrogenase inhibitor), naltrexone (opioid antagonist), nalmefene (opioid antagonist). Promising current studies suggest the glutamatergic pathway and medications such as ketamine could have a hopeful future in the treatment of alcohol use disorder associated with affective disorders.