TY - JOUR T1 - 4-Methylmethcathinone(mephedrone): neuropharmacological effects of a designer stimulant of abuse JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.111.184119 SP - jpet.111.184119 AU - Gregory C Hadlock AU - Katy M Webb AU - Lisa M McFadden AU - Pei Wen Chu AU - Jonathan D Ellis AU - Scott C Allen AU - David M Andrenyak AU - Paula L Vieira-Brock AU - Christoper L German AU - Kevin M Conrad AU - Amanda J Hoonakker AU - James W Gibb AU - Diana G Wilkins AU - Glen R Hanson AU - Annette E Fleckenstein Y1 - 2011/01/01 UR - http://jpet.aspetjournals.org/content/early/2011/08/02/jpet.111.184119.abstract N2 - The designer stimulant, 4-methylmethcathinone (mephedrone), is among the most popular of the derivatives of the naturally occurring psychostimulant, cathinone. Mephedrone has been readily available for legal purchase both online and in some stores, and has been promoted by aggressive web-based marketing. Its abuse in many countries, including the United States, is a serious public health concern. Owing largely to its recent emergence, there are no formal pharmacodynamic or pharmacokinetic studies of mephedrone. Accordingly, the purpose of this study was to evaluate effects of this agent in a rat model. Results revealed that, similar to methylenedioxymethamphetamine, methamphetamine and methcathinone, repeated mephedrone injections (4 x 10 - 25 mg/kg/injection, s.c., 2-h intervals, administered in a pattern used frequently to mimic psychostimulant “binge” treatment) cause a rapid decrease in striatal dopamine (DA) and hippocampal serotonin (5-hydroxytryptamine; 5HT) transporter function. Mephedrone also inhibited both synaptosomal DA and 5HT uptake. Like methylenedioxymethamphetamine, but unlike methamphetamine or methcathinone, repeated mephedrone administrations also caused persistent serotonergic, but not dopaminergic, deficits. However, mephedrone caused DA release from a striatal suspension approaching that of methamphetamine, and was self-administered by rodents. A method was developed to assess mephedrone concentrations in rat brain and plasma, and mephedrone levels were determined 1 h after a "binge" treatment. These data demonstrate that mephedrone has a unique pharmacological profile with both abuse liability and neurotoxic potential. ER -