Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells.
Linda D Simmler, Matthias E Liechti
Current Topics in Behavioral Neurosciences 2017 DOI: 10.1007/7854_2016_20 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Cathinones Efflux Heterologous expression systems In vitro New psychoactive substances Pharmacology Transporters Uptake |
| Key findings | Argues that in vitro assays in heterologous expression systems can predict the psychoactive and toxicological effects of cathinone NPS. Cathinones are monoamine uptake inhibitors, most also induce transporter-mediated monoamine efflux, and pyrrolidine-ring cathinones are extremely potent transporter inhibitors but not releasers. The authors contend that cathinones' greater dopaminergic versus serotonergic profile relative to non-β-keto amphetamines suggests more stimulant and reinforcing properties. |
Abstract
Pharmacological assays carried out in transfected cells have been very useful for describing the mechanism of action of cathinone new psychoactive substances (NPS). These in vitro characterizations provide fast and reliable information on psychoactive substances soon after they emerge for recreational use. Well-investigated comparator compounds, such as methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, and lysergic acid diethylamide, should always be included in the characterization to enhance the translation of the in vitro data into clinically useful information. We classified cathinone NPS according to their pharmacology at monoamine transporters and receptors. Cathinone NPS are monoamine uptake inhibitors and most induce transporter-mediated monoamine efflux with weak to no activity at pre- or postsynaptic receptors. Cathinones with a nitrogen-containing pyrrolidine ring emerged as NPS that are extremely potent transporter inhibitors but not monoamine releasers. Cathinones exhibit clinically relevant differences in relative potencies at serotonin vs. dopamine transporters. Additionally, cathinone NPS have more dopaminergic vs. serotonergic properties compared with their non-β-keto amphetamine analogs, suggesting more stimulant and reinforcing properties. In conclusion, in vitro pharmacological assays in heterologous expression systems help to predict the psychoactive and toxicological effects of NPS.