title: 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse.
abstract: 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× 10 or 25 mg/kg s.c. per injection, 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Hadlock
authors.forename: Katy M
authors.initials: KM
authors.lastname: Webb
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McFadden
authors.forename: Pei Wen
authors.initials: PW
authors.lastname: Chu
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Ellis
authors.forename: Scott C
authors.initials: SC
authors.lastname: Allen
authors.forename: David M
authors.initials: DM
authors.lastname: Andrenyak
authors.forename: Paula L
authors.initials: PL
authors.lastname: Vieira-Brock
authors.forename: Christopher L
authors.initials: CL
authors.lastname: German
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Conrad
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hoonakker
authors.forename: James W
authors.initials: JW
authors.lastname: Gibb
authors.forename: Diana G
authors.initials: DG
authors.lastname: Wilkins
authors.forename: Glen R
authors.initials: GR
authors.lastname: Hanson
authors.forename: Annette E
authors.initials: AE
authors.lastname: Fleckenstein
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015198:Designer Drugs / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000633:toxicity; D011634:Public Health; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012701:Serotonin / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D015198:Designer Drugs; D018765:Dopamine Uptake Inhibitors; D012701:Serotonin; D008694:Methamphetamine; C548233:mephedrone; D004298:Dopamine