Bath Salts: A Synthetic Cathinone Whose Two Major Components Act Similar to Methamphetamine and Cocaine on the Human Dopamine Transporter

Abstract

β-Keto-amphetamine analogs (synthetic cathinones) represent a new and rapidly growing class of abused substances. Members include cathinone (khat) and the mixture of mephedrone and MDPV (bath salts), which is increasingly popular in the United States. Similar to amphetamine and methamphetamine, cathinone and methcathinone work primarily at the dopamine transporter (DAT) as dopamine (DA) releasing agents and CNS stimulants. Theoretically, hundreds of synthetic cathinones are structurally possible, and more than a dozen analogs have been designated as illegal. With few exceptions, however, little is known about the pharmacology or mechanism of these new and powerful drugs. Furthermore, most cathinone analogs are unavailable in pure form for scientific investigation. We are synthesizing racemic mixtures and optical isomers of synthetic cathinones, some of which are already on the clandestine market, to investigate their pharmacology and mechanism of action. Electrophysiological studies of bath salts on hDAT-expressing frog oocytes show that one component, mephedrone, has an electrical signature similar to methamphetamine, while another component, MDPV, has the electrical signature of cocaine. In particular, 10 μM mephedrone elicits an inward current at −60 mV that persists long after the drug is removed externally, similar to the molecular stent mechanism described for S(+)Amphetamine (Rodriguez-Menchaca et al., British J Pharmocology, 2011). MDPV on the other hand elicits an outward current under similar conditions, indicative of a blocking agent similar to cocaine. We have verified MDPV block of hDAT in 3H-DA uptake experiments. Our results indicate that bath salts contain a DA releasing agent and a DA reuptake inhibitor. The two drugs have different kinetics and rather than cancel each other they would exacerbate the effect of either drug applied alone.