The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.
Bryan L. Roth, Simon Gibbons, Warunya Arunotayanun, Xi-Ping Huang, Vincent Setola, Ric Treble, Les Iversen
PLoS One June 14, 2016 DOI: 10.1371/journal.pone.0059334 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacological profiling Peer reviewed |
|---|---|
| Topics | 5-MeO-DMT Esketamine Ketamine |
| Citations | 153 |
| Key points | Novel ketamine and phencyclidine analogues are high-affinity ligands for the NMDA receptor PCP-site, which may account for their psychotomimetic effects in humans. |
Abstract
In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS)-2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine), were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
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- Designer drugs: mechanism of action and adverse effects Archives of Toxicology April 1, 2020
- From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis 2014
- Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacology & Therapeutics July 1, 2019
- Legal highs: staying on top of the flood of novel psychoactive substances Therapeutic Advances in Psychopharmacology January 26, 2015
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Cites 8
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- Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine Human Psychopharmacology: Clinical and Experimental March 1, 2012
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- Methoxetamine associated reversible cerebellar toxicity: Three cases with analytical confirmation Clinical Toxicology May 11, 2012
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