Academic literature on the topic 'Norketamine'
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Journal articles on the topic "Norketamine"
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Yeh, Chung-Hsin, Bo-He Chen, Xiao-Wen Tseng, Chun-Hou Liao, Wei-Kung Tsai, Han-Sun Chiang, and Yi-No Wu. "Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats." Toxics 9, no. 7 (June 30, 2021): 154. http://dx.doi.org/10.3390/toxics9070154.
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This study aimed to determine the mechanism of ketamine-induced cystitis without metabolism. A total of 24 adult male Sprague-Dawley rats were separated into control, ketamine, and norketamine groups. To induce cystitis, rats in the ketamine and norketamine groups were treated with intravesical instillation of ketamine and norketamine by mini-osmotic pump, which was placed in subcutaneous space, daily for 24 h for 4 weeks. After 4 weeks, all rats were subjected to bladder functional tests. The bladders were collected for histological and pathological evaluation. Compared to control, ketamine treatment demonstrated an increase in the bladder weight, high bladder/body coefficient, contractive pressure, voiding volume, collagen deposition, reduced smooth muscle content, damaged glycosaminoglycan layer, and low bladder compliance. Compared to ketamine, norketamine treatment showed more severe collagen deposition, smooth muscle loss, damaged glycosaminoglycan layer, and increased residual urine. Intravesical administration of ketamine and norketamine induced cystitis with different urodynamic characteristics. Norketamine treatment caused more severe bladder dysfunction than ketamine treatment. Direct treatment of the bladder with norketamine induced symptoms more consistent with those of bladder outlet obstruction than ketamine cystitis. Detailed studies of cellular mechanisms are required to determine the pathogenesis of ketamine cystitis.
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Noppers, Ingeborg, Erik Olofsen, Marieke Niesters, Leon Aarts, René Mooren, Albert Dahan, Evan Kharasch, and Elise Sarton. "Effect of Rifampicin on S-ketamine and S-norketamine Plasma Concentrations in Healthy Volunteers after Intravenous S-ketamine Administration." Anesthesiology 114, no. 6 (June 1, 2011): 1435–45. http://dx.doi.org/10.1097/aln.0b013e318218a881.
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Background Low-dose ketamine is used as analgesic for acute and chronic pain. It is metabolized in the liver to norketamine via cytochrome P450 (CYP) enzymes. There are few human data on the involvement of CYP enzymes on the elimination of norketamine and its possible contribution to analgesic effect. The aim of this study was to investigate the effect of CYP enzyme induction by rifampicin on the pharmacokinetics of S-ketamine and its major metabolite, S-norketamine, in healthy volunteers. Methods Twenty healthy male subjects received 20 mg/70 kg/h (n = 10) or 40 mg/70 kg/h (n = 10) intravenous S-ketamine for 2 h after either 5 days oral rifampicin (once daily 600 mg) or placebo treatment. During and 3 h after drug infusion, arterial plasma concentrations of S-ketamine and S-norketamine were obtained at regular intervals. The data were analyzed with a compartmental pharmacokinetic model consisting of three compartments for S-ketamine, three sequential metabolism compartments, and two S-norketamine compartments using the statistical package NONMEM® 7 (ICON Development Solutions, Ellicott City, MD). Results Rifampicin caused a 10% and 50% reduction in the area-under-the-curve of the plasma concentrations of S-ketamine and S-norketamine, respectively. The compartmental analysis indicated a 13% and 200% increase in S-ketamine and S-norketamine elimination from their respective central compartments by rifampicin. Conclusions : A novel observation is the large effect of rifampicin on S-norketamine concentrations and indicates that rifampicin induces the elimination of S-ketamine's metabolite, S-norketamine, probably via induction of the CYP3A4 and/or CYP2B6 enzymes.
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Olofsen, Erik, Ingeborg Noppers, Marieke Niesters, Evan Kharasch, Leon Aarts, Elise Sarton, and Albert Dahan. "Estimation of the Contribution of Norketamine to Ketamine-induced Acute Pain Relief and Neurocognitive Impairment in Healthy Volunteers." Anesthesiology 117, no. 2 (August 1, 2012): 353–64. http://dx.doi.org/10.1097/aln.0b013e31825b6c91.
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Background The N-methyl-D-aspartate receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. One approach to assess the ketamine and norketamine contributions is by measuring the ketamine effect at varying ketamine and norketamine plasma concentrations using the CYP450 inducer rifampicin. Methods In 12 healthy male volunteers the effect of rifampicin versus placebo pretreatment on S-ketamine-induced analgesia and cognition was quantified; the S-ketamine dosage was 20 mg/h for 2 h. The relative ketamine and norketamine contribution to effect was estimated using a linear additive population pharmacokinetic-pharmacodynamic model. Results S-ketamine produced significant analgesia, psychotropic effects (drug high), and cognitive impairment (including memory impairment and reduced psychomotor speed, reaction time, and cognitive flexibility). Modeling revealed a negative contribution of S-norketamine to S-ketamine- induced analgesia and absence of contribution to cognitive impairment. At ketamine and norketamine effect concentrations of 100 ng/ml and 50 ng/ml, respectively, the ketamine contribution to analgesia is -3.8 cm (visual analog pain score) versus a contribution of norketamine of +1.5 cm, causing an overall effect of -2.3 cm. The blood-effect site equilibration half-life ranged from 0 (cognitive flexibility) to 11.8 (pain intensity) min and was 6.1 min averaged across all endpoints. Conclusions This first observation that norketamine produces effects in the opposite direction of ketamine requires additional proof. It can explain the observation of ketamine-related excitatory phenomena (such as hyperalgesia and allodynia) upon the termination of ketamine infusions.
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Goldberg, Michael E. "Pharmacodynamic Profiles of Ketamine (R)- and (S)- with 5-Day Inpatient Infusion for the Treatment of Complex Regional Pain Syndrome." Pain Physician 4;13, no. 4;7 (July 14, 2010): 379–87. http://dx.doi.org/10.36076/ppj.2010/13/379.
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Background: Ketamine might be effective in blocking central sensitization of pain transmission neurons through its effect on NMDA receptors in refractory Complex Regional Pain Syndrome (CRPS) patients. At higher doses, ketamine infusions can be associated with significant risks; outpatient therapy requires return visits for a 10-day period with variable efficacy and duration. Objective: This study determined the efficacy of a 5-day moderate dose, continuous racemic ketamine infusion. The pharmacodynamic responses to racemic ketamine and norketamine were examined. Design: Observational study Methods: In this study, ketamine was titrated from 10-40 mg/hour in 16 CRPS patients, and maintained for 5 days. Pain was assessed daily. Ketamine and norketamine concentrations were obtained on Day 1 before starting the infusion; at 60 to 90 minutes, 120 to 150 minutes, 180 to 210 minutes, and 240 to 300 minutes after the initiation of the infusion on Days 2, 3, 4, and 5; and on Day 5 at 60 minutes after the conclusion of the infusion. The plasma concentrations of (R)-ketamine, (S)-ketamine, (R)-norketamine and (S)-norketamine were determined using an enantioselective liquid chromatography – mass spectrometry method. Results: Ketamine and norketamine infusion rates stabilized 5 hours after the start of the infusion. The subjects showed no evidence of significant tachycardia, arterial oxygen desaturation, or hallucinatory responses. Subjects generally experienced minimal pain relief on day one followed by significant relief by day 3. Mean pain scores decreased from the 8-9 to 3-5 ranges; however, the analgesic response to ketamine infusion was not uniform. On day 5, there was little or no change in the pain measure assessed as the worst pain experienced over the last 24 hours in 37% of the subjects. (R)- and (S)-ketamine concentrations peaked at 240-300 min. (R)- and (S)-norketamine concentrations were lower and peaked on Day 2 of the infusion, as opposed to Day 1 for (R)- and (S)-ketamine. Significant pain relief was achieved by the second day of infusion and correlated with the maximum plasma levels of ketamine and norketamine. Pain relief continued to significantly improve over the 5 day infusion at concentrations of 200-225 ng/mL for (R)- and (S)-ketamine, and 90-120 ng/mL for(R)- and (S)-norketamine. Conclusions: A 5-day ketamine infusion for the treatment of severe CRPS provided significant (P <0.05) pain relief by Day 3 compared to baseline. The pain relief experienced on Day 2 of the infusion continued to improve over the 5-day infusion period and correlated with the maximum plasma levels of ketamine and norketamine. We speculate that downstream metabolites of ketamine and norketamine might be playing a role in its therapeutic efficacy. Key words: ketamine, norketamine, CRPS, pharmacodynamics, chronic pain, enantiomers
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Ahmad, Samir M., Mariana N. Oliveira, Nuno R. Neng, and J. M. F. Nogueira. "A Fast and Validated High Throughput Bar Adsorptive Microextraction (HT-BAµE) Method for the Determination of Ketamine and Norketamine in Urine Samples." Molecules 25, no. 6 (March 22, 2020): 1438. http://dx.doi.org/10.3390/molecules25061438.
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We developed, optimized and validated a fast analytical cycle using high throughput bar adsorptive microextraction and microliquid desorption (HT-BAμE-μLD) for the extraction and desorption of ketamine and norketamine in up to 100 urine samples simultaneously, resulting in an assay time of only 0.45 min/sample. The identification and quantification were carried out using large volume injection-gas chromatography-mass spectrometry operating in the selected ion monitoring mode (LVI-GC-MS(SIM)). Several parameters that could influencing HT-BAµE were assayed and optimized in order to maximize the recovery yields of ketamine and norketamine from aqueous media. These included sorbent selectivity, desorption solvent and time, as well as shaking rate, microextraction time, matrix pH, ionic strength and polarity. Under optimized experimental conditions, suitable sensitivity (1.0 μg L−1), accuracy (85.5–112.1%), precision (≤15%) and recovery yields (84.9–105.0%) were achieved. Compared to existing methods, the herein described analytical cycle is much faster, environmentally friendly and cost-effective for the quantification of ketamine and norketamine in urine samples. To our knowledge, this is the first work that employs a high throughput based microextraction approach for the simultaneous extraction and subsequent desorption of ketamine and norketamine in up to 100 urine samples simultaneously.
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Le Nedelec, Martin, Paul Glue, Helen Winter, Chelsea Goulton, and Natalie J. Medlicott. "The effect of route of administration on the enantioselective pharmacokinetics of ketamine and norketamine in rats." Journal of Psychopharmacology 32, no. 10 (June 13, 2018): 1127–32. http://dx.doi.org/10.1177/0269881118780013.
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Background: Ketamine has been shown to produce a rapid and potent antidepressant response in patients with treatment-resistant depression. Currently ketamine is most commonly administered as a 40-minute intravenous infusion, though it is unknown whether this is the optimal route of administration. Aims: To determine the plasma concentration time course of the R- and S-enantiomers of ketamine and norketamine following administration of ketamine by four different routes of administration. Methods: Plasma from conscious non-anaesthetised rats was collected following administration of ketamine by either subcutaneous (SC), intramuscular (IM), intravenous infusion (IVI) or intravenous bolus (IVB) routes of administration. Concentrations of the enantiomers of ketamine and norketamine were determined by LC/MS. Results: Administration by the SC, IM and IVI routes produced an overall similar drug exposure. In contrast, administration by the IVB route produced approximately 15-fold higher peak plasma concentrations for the enantiomers of ketamine and an approximately four-fold lower AUC for the enantiomers of norketamine. Conclusions: Route of administration can significantly influence ketamine and norketamine exposures. These differences may influence safety and tolerability, and potentially drug efficacy in humans. This knowledge adds to current research into the optimisation of the use of ketamine for the treatment of depression.
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Highland, Jaclyn N., Cristan A. Farmer, Panos Zanos, Jacqueline Lovett, Carlos A. Zarate, Ruin Moaddel, and Todd D. Gould. "Sex-dependent metabolism of ketamine and (2R,6R)-hydroxynorketamine in mice and humans." Journal of Psychopharmacology 36, no. 2 (December 31, 2021): 170–82. http://dx.doi.org/10.1177/02698811211064922.
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Background: Ketamine is rapidly metabolized to norketamine and hydroxynorketamine (HNK) metabolites. In female mice, when compared to males, higher levels of ( 2R,6R;2S,6S)-HNK have been observed following ketamine treatment, and higher levels of ( 2R,6R)-HNK following the direct administration of ( 2R,6R)-HNK. Aim: The objective of this study was to evaluate the impact of sex in humans and mice, and gonadal hormones in mice on the metabolism of ketamine to form norketamine and HNKs and in the metabolism/elimination of ( 2R,6R)-HNK. Methods: In CD-1 mice, we utilized gonadectomy to evaluate the role of circulating gonadal hormones in mediating sex-dependent differences in ketamine and ( 2R,6R)-HNK metabolism. In humans (34 with treatment-resistant depression and 23 healthy controls) receiving an antidepressant dose of ketamine (0.5 mg/kg i.v. infusion over 40 min), we evaluated plasma levels of ketamine, norketamine, and HNKs. Results: In humans, plasma levels of ketamine and norketamine were higher in males than females, while ( 2R,6R;2S,6S)-HNK levels were not different. Following ketamine administration to mice (10 mg/kg i.p.), Cmax and total plasma concentrations of ketamine and norketamine were higher, and those of ( 2R,6R;2S,6S)-HNK were lower, in intact males compared to females. Direct ( 2R,6R)-HNK administration (10 mg/kg i.p.) resulted in higher levels of ( 2R,6R)-HNK in female mice. Ovariectomy did not alter ketamine metabolism in female mice, whereas orchidectomy recapitulated female pharmacokinetic differences in male mice, which was reversed with testosterone replacement. Conclusion: Sex is an important biological variable that influences the metabolism of ketamine and the HNKs, which may contribute to sex differences in therapeutic antidepressant efficacy or side effects.
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Sigtermans, Marnix, Albert Dahan, René Mooren, Martin Bauer, Benjamin Kest, Elise Sarton, and Erik Olofsen. "S(+)-ketamine Effect on Experimental Pain and Cardiac Output." Anesthesiology 111, no. 4 (October 1, 2009): 892–903. http://dx.doi.org/10.1097/aln.0b013e3181b437b1.
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Background Low-dose ketamine behaves as an analgesic in the treatment of acute and chronic pain. To further understand ketamine's therapeutic profile, the authors performed a population pharmacokinetic-pharmacodynamic analysis of the S(+)-ketamine analgesic and nonanalgesic effects in healthy volunteers. Methods Ten men and ten women received a 2-h S(+)-ketamine infusion. The infusion was increased at 40 ng/ml per 15 min to reach a maximum of 320 ng/ml. The following measurements were made: arterial plasma S(+)-ketamine and S(+)-norketamine concentrations, heat pain intensity, electrical pain tolerance, drug high, and cardiac output. The data were modeled by using sigmoid Emax models of S(+)-ketamine concentration versus effect and S(+)-ketamine + S(+)-norketamine concentrations versus effect. Results Sex differences observed were restricted to pharmacokinetic model parameters, with a 20% greater elimination clearance of S(+)-ketamine and S(+)-norketamine in women resulting in higher drug plasma concentrations in men. S(+)-ketamine produced profound drug high and analgesia with six times greater potency in the heat pain than the electrical pain test. After ketamine-infusion, analgesia rapidly dissipated; in the heat pain test but not the electrical pain test, analgesia was followed by a period of hyperalgesia. Over the dose range tested, ketamine produced a 40-50% increase in cardiac output. A significant consistent contribution of S(+)-norketamine to overall effect was detected for none of the outcome parameters. Conclusions S(+)-ketamine displays clinically relevant sex differences in its pharmacokinetics. It is a potent analgesic at already low plasma concentrations, but it is associated with intense side effects.
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Swartjes, Maarten, Aurora Morariu, Marieke Niesters, Leon Aarts, and Albert Dahan. "Nonselective and NR2B-selective N -methyl-d-aspartic Acid Receptor Antagonists Produce Antinociception and Long-term Relief of Allodynia in Acute and Neuropathic Pain." Anesthesiology 115, no. 1 (July 1, 2011): 165–74. http://dx.doi.org/10.1097/aln.0b013e31821bdb9b.
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Background At low dose, the nonselective N-methyl-D-aspartate receptor antagonist ketamine produces potent analgesia. In humans, psychedelic side effects limit its use. To assess whether other N-methyl-D-aspartate receptor antagonist have an improved therapeutic utility index, we compared antinociceptive, side effect, and locomotor activity of three N-methyl-D-aspartate receptor antagonists. Methods Ketamine, its active metabolite norketamine, and the NR2B-selective antagonist traxoprodil (CP-101,606) were tested in rat models of acute antinociception (paw-withdrawal response to heat) and chronic neuropathic pain (spared nerve injury). Side effects (stereotypical behavior, activity level) were scored and locomotor function of the nerve-injured paw was assessed using computerized gait analysis. In the chronic pain model, treatment was given 7 days after surgery, for 3 h on 5 consecutive days. Results All three N-methyl-D-aspartate receptor antagonists caused dose-dependent antinociception in the acute pain model and relief of mechanical and cold allodynia for 3-6 weeks after treatment in the chronic pain model (P < 0.05 vs. saline). In both tests, ketamine was most potent. Norketamine was as much as two times less potent and traxoprodil was up to 8 times less potent than ketamine (based on area under the curve measures). Nerve injury caused an inability to use the affected paw that either did not improve after treatment (ketamine, traxoprodil) or showed only a limited effect (norketamine). Traxoprodil, but not ketamine or norketamine, showed clear separation between effect and side effect. Conclusions The observation that traxoprodil causes relief of chronic pain outlasting the treatment period with no side effects makes it an attractive alternative to ketamine in the treatment of chronic neuropathic pain.
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Paul, Rajib K., Nagendra S. Singh, Mohammed Khadeer, Ruin Moaddel, Mitesh Sanghvi, Carol E. Green, Kathleen O’Loughlin, Marc C. Torjman, Michel Bernier, and Irving W. Wainer. "(R,S)-Ketamine Metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine Increase the Mammalian Target of Rapamycin Function." Anesthesiology 121, no. 1 (July 1, 2014): 149–59. http://dx.doi.org/10.1097/aln.0000000000000285.
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Abstract Background: Subanesthetic doses of (R,S)-ketamine are used in the treatment of neuropathic pain and depression. In the rat, the antidepressant effects of (R,S)-ketamine are associated with increased activity and function of mammalian target of rapamycin (mTOR); however, (R,S)-ketamine is extensively metabolized and the contribution of its metabolites to increased mTOR signaling is unknown. Methods: Rats (n = 3 per time point) were given (R,S)-ketamine, (R,S)-norketamine, and (2S,6S)-hydroxynorketamine and their effect on the mTOR pathway determined after 20, 30, and 60 min. PC-12 pheochromocytoma cells (n = 3 per experiment) were treated with escalating concentrations of each compound and the impact on the mTOR pathway was determined. Results: The phosphorylation of mTOR and its downstream targets was significantly increased in rat prefrontal cortex tissue by more than ~2.5-, ~25-, and ~2-fold, respectively, in response to a 60-min postadministration of (R,S)-ketamine, (R,S)-norketamine, and (2S,6S)-hydroxynorketamine (P < 0.05, ANOVA analysis). In PC-12 pheochromocytoma cells, the test compounds activated the mTOR pathway in a concentration-dependent manner, which resulted in a significantly higher expression of serine racemase with ~2-fold increases at 0.05 nM (2S,6S)-hydroxynorketamine, 10 nM (R,S)-norketamine, and 1,000 nM (R,S)-ketamine. The potency of the effect reflected antagonistic activity of the test compounds at the α7-nicotinic acetylcholine receptor. Conclusions: The data demonstrate that (R,S)-norketamine and (2S,6S)-hydroxynorketamine have potent pharmacological activity both in vitro and in vivo and contribute to the molecular effects produced by subanesthetic doses of (R,S)-ketamine. The results suggest that the determination of the mechanisms underlying the antidepressant and analgesic effects of (R,S)-ketamine requires a full study of the parent compound and its metabolites.
Dissertations / Theses on the topic "Norketamine"
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Porpiglia, Nadia Maria. "Electrophoretic methods in tubular microcompartments – forensic applications of capillary electrophoresis (CE) and CE coupled to mass spectrometry (MS)." Doctoral thesis, 2017. http://hdl.handle.net/11562/963251.
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Forensic science is a peculiar scientific discipline that includes all those scientific technologies and applications that are valuable to support the forensic investigation and/or to bring scientific evidence to court. On many occasions, forensic science provides also the information needed for drafting new laws and rules requiring scientific knowledge [1-3]. The main areas of this discipline are forensic toxicology, analysis of explosives, gunshot residues and chemical warfare, trace analysis (fibres, hairs, inks, dyes, glass etc.), and forensic genetics. For the latter area, which is based on DNA fragment analysis and sequencing, the development of capillary electrophoresis (CE) technology has been a fundamental step forward [4], being today a standard technique worldwide. In almost all its fields of application, the development of analytical forensic sciences finds two milestones: i. the introduction of chromatography and electrophoresis and ii., more recently, the introduction of mass spectrometric techniques. In both chromatography and electrophoresis, the miniaturisation of the separation compartment in a capillary format has highly increased the analytical efficiency and improved the possibility of coupling with mass spectrometry (MS). In the recent decades, CE proved to be a powerful analytical technique because of its excellent separation efficiency, high resolution and selectivity, short analysis time, low reagent consumption, sample volume and cost, and good recovery [5]. In particular, when performing enantioselective analyses, CE is known for being one of the most favoured separation techniques due to its numerous advantages listed above [6]. On these grounds, the major aims of the present doctoral research project were i. to improve and to develop analytical methods in CE for the stereoselective separations of NPSs (New Psychoactive Substances) and of drugs involved in dependence withdrawal therapy; ii. to couple CE with MS in order to improve analytical sensitivity and selectivity. With regards to i., a CZE (Capillary Zone Electrophoresis) method was developed for the chiral separation of ketamine and its major metabolite, norketamine, in hair specimens, in order to investigate potential chronic abuses in the context of traffic and workplace law enforcement. Moreover, an existing analytical method for the measurement of baclofen was further improved, being baclofen a drug that proved effective when administered to alcohol dependent patients in order to reduce the severe symptoms of sudden withdrawal from alcohol abuse. Last-but-not-least, CE, originally equipped with a UV detector, was coupled to a TOF (Time Of Flight) mass spectrometer with the purpose of taking advantage from the unique features of this mass spectrometry technique, i.e. possibility of acquisition of the “total ion current” without sacrificing sensitivity, possibility of re-processing of the raw data for post-analysis search of compounds, high speed of data acquisition. Moreover, since forensic toxicology involves complex biological matrices, the matrix effect was investigated with the aim of evaluating the possible advantages on ion suppression offered by a miniaturised separation technique, such as CE.
Books on the topic "Norketamine"
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Thwaites, Rosemary Elizabeth. Plasma concentrations of ketamine and norketamine and their correlation with pain relief in post-herpetic neuralgia. 1994.
Find full textBook chapters on the topic "Norketamine"
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Fallon, Marie, Cameron Fergus, and Barry J. A. Laird. "Ketamine and other NMDA receptor antagonists." In Neuropathic Pain, 115–24. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199563678.003.0013.
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Ketamine is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist and is most effective in pain states where hyper-excitability is established Ketamine undergoes first-pass metabolism to norketamine, which is a more potent analgesic than ketamine. This can explain why oral ketamine is more potent than parenteral ketamine...
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"Norketamin." In Springer Reference Medizin, 1760. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_312756.
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Lopuh, Mateja. "Use of Oral Ketamine in Palliative Care." In Ketamine Revisited - New Insights into NMDA Inhibitors [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.104875.
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Ketamine, an N-methyl-D-Aspartate receptor antagonist, has been used for more than 50 years. From its initial potential as an anesthetic drug, its use has increased in the fields of pain medicine, psychiatry, and palliative care. It is available in different formulations, of which oral use is promising due to its active metabolite, norketamine which reaches 2–3 times higher levels when administered orally in comparison with parenteral use. Oral use is also more feasible and easier to use in settings, where medical staff is not that present, such as home care or hospices. Oral solution of ketamine has not yet been officially licensed for use although there have been several reports which recommend its use in neuropathic pain, severe depression, airway obstruction, and anxiety. Palliative care is defined as total care for patients whose diseases do not respond to curative treatment. It encompasses good control of physical symptoms, and psychological, social and spiritual problems. Patients often experience pain, despite high doses of opioids, depression and anxiety, and dyspnea. Oral ketamine does not have the side effects of opioids therefore it represents a good alternative. It may also reduce the need for high opioid doses and be more suitable for patients who wish to avoid the necessary sedation.