Pharmacological characterization of designer cathinones in vitro
Article first published online: 20 DEC 2012
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society
British Journal of Pharmacology
Special Issue: Themed Section: Endothelin. Guest Editors: Anthony P Davenport and Matthias Barton
Volume 168, Issue 2, pages 458–470, January 2013
How to Cite
Simmler, L., Buser, T., Donzelli, M., Schramm, Y., Dieu, L.-H., Huwyler, J., Chaboz, S., Hoener, M. and Liechti, M. (2013), Pharmacological characterization of designer cathinones in vitro. British Journal of Pharmacology, 168: 458–470. doi: 10.1111/j.1476-5381.2012.02145.x
- Issue published online: 20 DEC 2012
- Article first published online: 20 DEC 2012
- Accepted manuscript online: 17 AUG 2012 05:22AM EST
- Manuscript Accepted: 8 AUG 2012
- Manuscript Revised: 30 JUL 2012
- Manuscript Received: 4 JUL 2012
- Swiss National Science Foundation. Grant Numbers: 323230_126231, 3232B_144996
- Translational Medicine Hub Innovation Fund of F Hoffmann-La Roche and the University of Basel
- designer drug;
- legal high;
- monoamine transporter;
Background and Purpose
Designer β-keto amphetamines (e.g. cathinones, ‘bath salts’ and ‘research chemicals’) have become popular recreational drugs, but their pharmacology is poorly characterized.
We determined the potencies of cathinones to inhibit DA, NA and 5-HT transport into transporter-transfected HEK 293 cells, DA and 5-HT efflux from monoamine-preloaded cells, and monoamine receptor binding affinity.
Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and other entactogens. Cathinone, methcathinone and flephedrone, similar to amphetamine and methamphetamine, acted as preferential DA and NA uptake inhibitors and induced the release of DA. Pyrovalerone and 3,4-methylenedioxypyrovalerone (MDPV) were highly potent and selective DA and NA transporter inhibitors but unlike amphetamines did not evoke the release of monoamines. The non-β-keto amphetamines are trace amine-associated receptor 1 ligands, whereas the cathinones are not. All the cathinones showed high blood–brain barrier permeability in an in vitro model; mephedrone and MDPV exhibited particularly high permeability.
Conclusions and Implications
Cathinones have considerable pharmacological differences that form the basis of their suggested classification into three groups. The predominant action of all cathinones on the DA transporter is probably associated with a considerable risk of addiction.