Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data?

Laura Hondebrink; Anne Zwartsen; Remco H S Westerink

doi:10.1016/j.pharmthera.2017.10.022

Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data?

Pharmacol Ther. 2018 Feb:182:193-224. doi: 10.1016/j.pharmthera.2017.10.022. Epub 2017 Oct 31.

Authors

Laura Hondebrink¹, Anne Zwartsen², Remco H S Westerink³

Affiliations

¹ Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht University, The Netherlands.
² Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht University, The Netherlands; Neurotoxicology Research Group, Division Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht, The Netherlands.
³ Neurotoxicology Research Group, Division Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht, The Netherlands. Electronic address: r.westerink@uu.nl.

PMID: 29097307
DOI: 10.1016/j.pharmthera.2017.10.022

Abstract

The use of new psychoactive substances (NPS) is increasing and currently >600 NPS have been reported. However, limited information on neuropharmacological and toxicological effects of NPS is available, hampering risk characterization. We reviewed the literature on the in vitro neuronal modes of action to obtain effect fingerprints of different classes of illicit drugs and NPS. The most frequently reported NPS were selected for review: cathinones (MDPV, α-PVP, mephedrone, 4-MEC, pentedrone, methylone), cannabinoids (JWH-018), (hallucinogenic) phenethylamines (4-fluoroamphetamine, benzofurans (5-APB, 6-APB), 2C-B, NBOMes (25B-NBOMe, 25C-NBOMe, 25I-NBOMe)), arylcyclohexylamines (methoxetamine) and piperazine derivatives (mCPP, TFMPP, BZP). Our effect fingerprints highlight the main modes of action for the different NPS studied, including inhibition and/or reversal of monoamine reuptake transporters (cathinones and non-hallucinogenic phenethylamines), activation of 5-HT₂receptors (hallucinogenic phenethylamines and piperazines), activation of cannabinoid receptors (cannabinoids) and inhibition of NDMA receptors (arylcyclohexylamines). Importantly, we identified additional targets by relating reported effect concentrations to the estimated human brain concentrations during recreational use. These additional targets include dopamine receptors, α- and β-adrenergic receptors, GABA_Areceptors and acetylcholine receptors, which may all contribute to the observed clinical symptoms following exposure. Additional data is needed as the number of NPS continues to increase. Also, the effect fingerprints we have obtained are still incomplete and suffer from a large variation in the reported effects and effect sizes. Dedicated in vitro screening batteries will aid in complementing specific effect fingerprints of NPS. These fingerprints can be implemented in the risk assessments of NPS that are necessary for eventual control measures to reduce Public Health risks.

Keywords: Designer drugs; mechanism of action; neuropharmacology; neurotoxicology; receptors; transporters.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Drug Evaluation, Preclinical / methods*
Humans
Models, Neurological
Psychotropic Drugs / adverse effects
Psychotropic Drugs / classification*
Psychotropic Drugs / pharmacology*

Substances

Psychotropic Drugs