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,L. L. Iversen +6 more
TLDR
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.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.read more
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A brief history of the development of antidepressant drugs: from monoamines to glutamate.
TL;DR: The noncompetitive NMDA receptor antagonist ketamine, which has consistently produced rapid and sustained antidepressant effects in MDD patients in a number of clinical studies, has shown the most promise as a novel glutamatergic-based treatment for MDD.
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From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs.
Hamilton Morris,Jason Wallach +1 more
TL;DR: The first complete portrait of this underground market is presented along with the relevant legal, technological, and scientific developments which have driven its evolution.
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Measuring biomarkers in wastewater as a new source of epidemiological information: Current state and future perspectives
Emma Gracia-Lor,Emma Gracia-Lor,Sara Castiglioni,Richard Bade,Frederic Been,Erika Castrignanò,Adrian Covaci,Iria González-Mariño,Evroula Hapeshi,Barbara Kasprzyk-Hordern,Juliet Kinyua,Foon Yin Lai,Thomas Letzel,Luigi Lopardo,Markus R. Meyer,Jake W. O'Brien,Pedram Ramin,Nikolaos I. Rousis,Axel Rydevik,Yeonsuk Ryu,Miguel M. Santos,Ivan Senta,Nikolaos S. Thomaidis,Sofia Veloutsou,Zhugen Yang,Ettore Zuccato,Lubertus Bijlsma +26 more
TL;DR: The current knowledge related to the most relevant biomarkers used so far in urban wastewater and information, when available, on stability in urine and wastewater and pharmacokinetic data has been reviewed.
Journal ArticleDOI
Next generation of novel psychoactive substances on the horizon - A complex problem to face.
TL;DR: This review presents updated information on the second generation of NPS, introduced as replacements of the already banned substances from this class, focusing on their pharmacological properties and metabolism, routes of administration, and effects in humans.
Journal ArticleDOI
Ketamine and phencyclidine: the good, the bad and the unexpected
D. Lodge,M S Mercier +1 more
TL;DR: The discovery in 1983 of the NMDA receptor antagonist property of ketamine and phencyclidine was a key step to understanding their pharmacology, including their psychotomimetic effects in man, and its expansion into other hallucinatory drugs.
References
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