“Polytox” synthetic cathinone abuse: A potential role for organic cation transporter 3 in combined cathinone-induced efflux

Publication date: Available online 21 September 2018Source: Neurochemistry InternationalAuthor(s): Felix P. Mayer, Diethart Schmid, Marion Holy, Lynette C. Daws, Harald H. SitteAbstractSynthetic cathinone derivatives are a new class of psychoactive substances (NPS), also known as “bath salts”, designed to exert psychostimulant effects resembling those of well-known psychostimulants, such as cocaine and 3,4-methylenedionxymethylamphetamine (MDMA, “ecstasy”). As major constituents of bath salts, the cathinone derivatives 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone), have received considerable media attention. MDPV and mephedrone interfere with the function of the high affinity transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT), resulting in increased extracellular levels of these monoamines, though their mechanism of action differs. MDPV acts as a powerful inhibitor of DAT, NET and SERT, whereas mephedrone promotes transporter-mediated release in an amphetamine-like fashion. MDPV and mephedrone are often taken together, creating a conundrum in as much as non-transported inhibitors, like MDPV, prevent mephedrone-induced reverse transport via DAT, NET and SERT. Here we provide evidence supporting a role for organic cation transporter 3 (OCT3) in the actions of mephedrone, which may account for its ability to enhance effects of MDPV, rather than block them. We show that mephedrone can induce substrate efflux via OCT3 ...
Source: Neurochemistry International - Category: Neuroscience Source Type: research