Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Dec 8;23(24):15574.
doi: 10.3390/ijms232415574.

Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects

Romain Pelletier  1   2 , Brendan Le Daré  1   3 , Diane Le Bouëdec  2 , Angéline Kernalléguen  1 , Pierre-Jean Ferron  1 , Isabelle Morel  1   2 , Thomas Gicquel  1   2
Affiliations
Review

Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects

Romain Pelletier et al. Int J Mol Sci. .

Abstract

Since the 2000s, an increasing number of new psychoactive substances (NPS) have appeared on the drug market. Arylcyclohexylamine (ACH) compounds such as ketamine, phencyclidine and eticyclidine derivatives are of particular concern, given their rapidly increasing use and the absence of detailed toxicity data. First used mainly for their pharmacological properties in anesthesia, their recreational use is increasing. ACH derivatives have an antagonistic activity against the N-methyl-D-aspartate receptor, which leads to dissociative effects (dissociation of body and mind). Synthetic ketamine derivatives produced in Asia are now arriving in Europe, where most are not listed as narcotics and are, thus, legal. These structural derivatives have pharmacokinetic and pharmacodynamic properties that are sometimes very different from ketamine. Here, we describe the pharmacology, epidemiology, chemistry and metabolism of ACH derivatives, and we review the case reports on intoxication.

Keywords: NPS; arylcyclohexylamines; ketamine; phencyclidine; review.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The ACH derivatives most frequently involved in cases of intoxication. PCP: phencyclidine (1-(1-phenylcyclohexyl)piperidine); DCK: deschlorokétamine (2-(methylamino)-2-phenylcyclohexan-1-one); PCE: eticyclidine (N-ethyl-1-phenylcyclohexan-1-amine); MXE: methoxetamine (2-(ethylamino)-2-(3-methoxyphenyl)cyclohexan-1-one); MXPr: methoxpropamine (2-(3-methoxyphenyl)-2-(propylamino)cyclohexan-1-one).
Figure 2
Figure 2
Mechanism of action of arylcyclohexylamine derivatives.
Figure 3
Figure 3
Overview of ketamine’s metabolism [26,45,46,51,52,53]; bold arrows indicate the major pathway and dotted arrows indicate minor metabolic pathways; FMO: flavin-containing monooxygenase.
Figure 4
Figure 4
Geographical distribution of published cases of ACH-derivative intoxication.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Shafi A., Berry A.J., Sumnall H., Wood D.M., Tracy D.K. New psychoactive substances: A review and updates. Ther. Adv. Psychopharmacol. 2020;10:2045125320967197. doi: 10.1177/2045125320967197. - DOI - PMC - PubMed
    1. Néfau T., Martinez M. Vol. 3 L’Observatoire Français des Drogues et Toxicomanies; Paris, France: 2000. Nouveaux Produits de Synthèse Identifiés en France Depuis 2000.
    1. Ameline A., Alvarez J.-C., Dumestre V., Eysseric H., Gaulier J.-M., Kintz P., Labat L., Lelievre B., Muckensturm A., Pélissier A.-L., et al. Recommandations de La SFTA Pour La Réalisation Des Analyses Toxicologiques Dans Les Cas de Décès Impliquant Des NPS – Version 2019 [SFTA Guidelines for the Achievement of Toxicological Analyzes for Deaths Involving NPS – 2019 Version] Toxicol. Anal. Clin. 2019;31:337–339. doi: 10.1016/j.toxac.2019.06.001. - DOI
    1. Johnstone M., Evans V., Baigel S. SERNYL (C1-395) IN CLINICAL ANAESTHESIA. Br. J. Anaesth. 1959;31:433–439. doi: 10.1093/bja/31.10.433. - DOI - PubMed
    1. Mion G. Histoire de la kétamine et du psychédélisme. Ann. Méd.-Psychol. Rev. Psychiatr. 2017;175:661–664. doi: 10.1016/j.amp.2017.07.002. - DOI

LinkOut - more resources