Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells.
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.
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
Linda D
LD
Simmler
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. matthias.liechti@usb.ch.
Matthias E
ME
Liechti
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000470:Alkaloids; D000697:Central Nervous System Stimulants; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C023665:cathinone
Cathinones; Efflux; Heterologous expression systems; In vitro; New psychoactive substances; Pharmacology; Transporters; Uptake