title: Stereoselective Effects of Abused "Bath Salt" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation.
abstract: 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit "bath salts" products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(-)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(-)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(-)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(-)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(-)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse.
authors.affiliation: Department of Pharmacology and Toxicology (B.M.G., W.E.F.), College of Medicine (A.W.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institutes of Health National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (M.S., K.C.R.).
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Gannon
authors.affiliation: Department of Pharmacology and Toxicology (B.M.G., W.E.F.), College of Medicine (A.W.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institutes of Health National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (M.S., K.C.R.).
authors.forename: Adrian
authors.initials: A
authors.lastname: Williamson
authors.affiliation: Department of Pharmacology and Toxicology (B.M.G., W.E.F.), College of Medicine (A.W.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institutes of Health National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (M.S., K.C.R.).
authors.forename: Masaki
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Pharmacology and Toxicology (B.M.G., W.E.F.), College of Medicine (A.W.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institutes of Health National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (M.S., K.C.R.).
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.affiliation: Department of Pharmacology and Toxicology (B.M.G., W.E.F.), College of Medicine (A.W.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institutes of Health National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (M.S., K.C.R.) WEFantegrossi@uams.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Fantegrossi
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000737:chemistry / Q000494:pharmacology*; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D015198:Designer Drugs / Q000737:chemistry / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D000094982:Synthetic Cathinone
chemical_list: D052117:Benzodioxoles; D015198:Designer Drugs; D011759:Pyrrolidines; D000094982:Synthetic Cathinone