title: Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates.
abstract: Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100-1000 μM) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 μM) and racemate (100 μM) produced EPC, but S-MEPH was ineffective at all concentrations (10-100 μM). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 μM) produced EPC that was abolished when S-MEPH (100 μM) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 μM) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10-250 μM). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own.
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vouga
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Gregg
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA.
authors.forename: Maryah
authors.initials: M
authors.lastname: Haidery
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Ramnath
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA.
authors.forename: Hassan K
authors.initials: HK
authors.lastname: Al-Hassani
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Tallarida
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Grizzanti
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Raffa
authors.affiliation: Fox Chase Chemical Diversity Center Inc., Doylestown, PA, USA.
authors.forename: Garry R
authors.initials: GR
authors.lastname: Smith
authors.affiliation: Fox Chase Chemical Diversity Center Inc., Doylestown, PA, USA.
authors.forename: Allen B
authors.initials: AB
authors.lastname: Reitz
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA. Electronic address: scott.rawls@temple.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009068:Movement / Q000187:drug effects*; D010932:Planarians; D012201:Reward; D013239:Stereotyped Behavior / Q000187:drug effects; D013375:Substance Withdrawal Syndrome
chemical_list: D008694:Methamphetamine; C548233:mephedrone; D003042:Cocaine
keywords: Addiction; Bath salt; Cathinone; Cocaine; Conditioned place preference; Enantiomer; Mephedrone; Planarians; Stereochemistry; Stereotypy; Withdrawal