Pharmacological characterization of designer cathinones in vitro

Background and purpose: Designer beta-keto amphetamines (e.g., cathinones, "bath salts," and "research chemicals") have become popular recreational drugs, but their pharmacology is poorly characterized. Experimental approach: We determined the potencies of cathinones to inhibit dopamine (DA), noradrenaline (NA), and serotonin (5-hydroxytryptamine [5-HT]) transport into transporter-transfected human embryonic kidney 293 cells, DA and 5-HT efflux from monoamine-preloaded cells, and monoamine receptor binding affinity. Key results: Mephedrone, methylone, ethylone, butylone, and naphyrone act as nonselective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone, and butylone also release 5-HT, similar to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and other entactogens. Cathinone, methcathinone, and flephedrone act as preferential DA and NA uptake inhibitors and DA releasers, similar to amphetamine and methamphetamine. Pyrovalerone and 3,4-methylenedioxypyrovalerone (MDPV) are highly potent and selective DA and NA transporter inhibitors but unlike amphetamines do not release monoamines. The non-beta-keto amphetamines are trace amine-associated receptor 1 ligands, whereas cathinones are not. All 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 for their suggested classification into three groups. The predominant action of all cathinones on the DA transporter is likely associated with a considerable risk of addiction. (c) 2012 The Authors. British Journal of Pharmacology (c) 2012 The British Pharmacological Society.