Effects of optical isomers of ketamine on excitation of cat and rat spinal neurones by amino acids and acetylcholine

Lodge, D; Anis, Nabil A.; Burton, N.R.

doi:10.1016/0304-3940(82)90330-5

Cited by 125 publications

(41 citation statements)

References 18 publications

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“…At low doses, it acts as a noncompetitive NMDAR antagonist that blocks the receptor by binding to a specific site at the NMDAR-gated ion channel [19,20]. Doses of ketamine higher than low analgesic doses can interact with several other receptors and ion channels, including opioid receptors, monoamine transporters, and dopamine D 2 receptors [21,22].…”

Section: Neurotoxic Effects Of Ketaminementioning

confidence: 99%

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

et al. 2016

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Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive Nmethyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fastacting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related sideeffects. Future treatment strategies should consider using Rketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.

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Section: Neurotoxic Effects Of Ketaminementioning

confidence: 99%

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

et al. 2016

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“…Since the 1980s, ketamine's mechanism of action has been considered to be mainly a noncompetitive antagonism of the N-methyl-D-aspartic acid (NMDA) receptor [6,7] . It was discovered in later research that ketamine also targets other receptors, such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and has additional acts as an agonist of the sigma 1 receptor [8] .…”

Section: Pharmacokinetics (Pk) and Pharmacodynamics (Pd)mentioning

confidence: 99%

Ketamine use in current clinical practice

2016

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After nearly half a century on the market, ketamine still occupies a unique corner in the medical armamentarium of anesthesiologists or clinicians treating pain. Over the last two decades, much research has been conducted highlighting the drug's mechanisms of action, specifically those of its enantiomers. Nowadays, ketamine is also being utilized for pediatric pain control in emergency department, with its anti-hyperalgesic and anti-inflammatory effects being revealed in acute and chronic pain management. Recently, new insights have been gained on ketamine's potential anti-depressive and antisuicidal effects. This article provides an overview of the drug's pharmacokinetics and pharmacodynamics while also discussing the potential benefits and risks of ketamine administration in various clinical settings.

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“…Specifically, both MK-801 {(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate)} and ketamine {2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone hydrochloride} have been shown to antagonize the excitatory [Lodge et al, 1982;Davies et al, 1987;Woodruff et al, 1987] and neurotoxic [Olney et al, 1987;Foster et al, 1987] properties of NMDA receptors. These findings are consistent with the hypothesis that NMDA receptors mediate most of the neurotoxicity caused by glutamate.…”

Section: Introductionmentioning

confidence: 99%

Effect of the Noncompetitive NMDA Antagonists MK-801 and Ketamine on the <i>Spastic</i> Han-Wistar Mutant: A Rat Model of Excitotoxicity

Brunson

Khanna²,

Cromwell³

et al. 2001

Dev Neurosci

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The neuroprotective effects of the NMDA antagonists MK-801 and ketamine were analyzed in a mutant strain of Han-Wistar rats which develop neurodegeneration in the hippocampus and cerebellum. Previous experiments have shown that the progressive neuronal degeneration observed in this mutant may be the result of a dysfunctional glutamatergic system. For MK-801 studies, mutants were injected in a chronic paradigm with (+)MK-801 or its weaker acting isomer (–)MK-801 at a dose of 1 mg/kg. Ketamine studies consisted of both acute (50 mg/kg once) and chronic (10 mg/kg multiple times) injection paradigms. MK-801-treated mutants exhibited longer life spans (8–23%) compared to saline-injected mutants. Ketamine-injected mutants in both paradigms also lived slightly longer (6–9%) than the saline mutants. Motor skill deterioration was monitored in an open-field test, and after 50 days of age the MK-801 and ketamine mutants displayed over 20% greater motor skill activity than the saline mutants. In the cerebellum, mutants treated with ketamine and both forms of MK-801 had 10–20% more Purkinje cells surviving at 55 days than the saline mutants. Further, the density of CA3c pyramidal hippocampal neurons in ketamine and MK-801-treated mutants as compared to saline mutants appeared to be greater upon qualitative analysis. This study shows that these mutants derive some protective effects from the NMDA antagonists MK-801 and ketamine, confirming glutamate-induced excitotoxicity as a possible cause of neuronal degeneration in this mutant strain of rat.

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Effects of optical isomers of ketamine on excitation of cat and rat spinal neurones by amino acids and acetylcholine

Cited by 125 publications

References 18 publications

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

Ketamine use in current clinical practice

Effect of the Noncompetitive NMDA Antagonists MK-801 and Ketamine on the <i>Spastic</i> Han-Wistar Mutant: A Rat Model of Excitotoxicity

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