Any queries (other than missing content) should be directed to the corresponding author for the article.Trust the Experienced Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. FilenameĪdb1239-Supplementary.docxWord 2007 document Symbols above ‘S” and ‘C’ represent the averages for all saline- and cocaine-training sessions preceding test sessions, respectively. Ordinate: percent cocaine-appropriate responding. Abscissae: time in minute after 4MMC injection. All compounds were tested in four rhesus monkeys.įigure S4: Cocaine-like discriminative stimulus effects of 4-methylmethcathinone, 4MMC, in individual male rhesus monkeys trained to discriminate cocaine (0.32 mg/kg, IM) from saline in a two-key food-reinforced discrimination procedure. ![]() Ordinate: percentage of monkeys in which full cocaine substitution occurred (≥90 percent cocaine-appropriate responding) at some time point for each test drug dose. Abscissa: drug dose (milligrams per kilogram, log scale). Filled symbols indicate statistical significance compared with saline at a given time point ( p < 0.05).įigure S3: Cocaine-like discriminative stimulus effects of (±)-alpha-pyrrolidinovalerophenone (alpha-PVP), (±)-methcathinone and their 3,4-methylenedioxy (3,4-methylenedioxypyrovalerone, MDPV 3,4-methylenedioxymethcathinone, MDMC) or 4-methyl (4-methylpyrrolidinovalerophenone, 4MPVP 4-methylmethcathinone, 4MMC) analogs in rhesus monkeys. Symbols above S and C represent the group averages for all saline- and cocaine-training sessions preceding test sessions, respectively. Ordinate: rates of responding in responses per second. Abscissae: time in minute after injection. Filled symbols indicate statistical significance compared with saline at a given time point ( p < 0.05).įigure S2: Effects of methcathinone (a) 3,4-methylenedioxymethcathinone (MDMC) (b) and 4-methylmethcathinone (4MMC) (c) on rates of operant responding in male rhesus monkeys trained to discriminate cocaine (0.32 mg/kg, IM) from saline in a two-key food-reinforced discrimination procedure. Symbols above ‘S” and ‘C” represent the group averages for all saline- and cocaine-training sessions preceding test sessions, respectively. Given that 4MMC is more hydrophobic than MDMC, these results suggest that hydrophobicity may be an important determinant for limiting monoamine transporter substrate abuse-related behavioral effects.įigure S1: Effects of alpha-pyrrolidinopentiophenone (alpha-PVP) (a) 3,4-methylenedioxypyrovalerone (MDPV) (b) and 4-methylpyrrolidinopentiophenone (4MPVP) (c) on rates of operant responding in male rhesus monkeys trained to discriminate cocaine from saline in a two-key food-reinforced discrimination procedure. Overall, these results suggest different structural requirements for cocaine-like discriminative stimulus effects of monoamine transporter inhibitor and substrate synthetic cathinone analogs. In contrast, addition of a 4-methyl moiety to methcathinone (4MMC mephedrone) significantly attenuated efficacy to produce cocaine-like effects. A 4-methyl addition to alpha-PVP (pyrovalerone) did not alter the potency or efficacy to produce cocaine-like effects, but did prolong the time course. ![]() A 3,4-methylenedioxy addition to either alpha-PVP or methcathinone (methylone) did not alter the potency or efficacy to produce cocaine-like effects, but did prolong the time course. Alpha-PVP and methcathinone produced dose- and time-dependent cocaine-like effects. Potency and timecourse of cocaine-like discriminative stimulus effects were determined for (±)-alpha-PVP, (±)-methcathinone and their 3,4-methylenedioxy or 4-methyl analogs. Male rhesus monkeys ( n = 4) were trained to discriminate intramuscular cocaine (0.32 mg/kg) from saline in a two-key food-reinforced discrimination procedure. The aim of the present study was to determine whether the cocaine-like discriminative stimulus effects of the monoamine transporter inhibitor alpha-pyrrolidinovalerophenone (alpha-PVP) and the monoamine transporter substrate methcathinone were differentially sensitive to 3,4-methylenedioxy and 4-methyl substitutions. Pre-clinical drug discrimination procedures are useful for interrogating structure–activity relationships of abuse-related drug effects however, in vivo structure–activity relationship comparisons between synthetic cathinones with different mechanisms of action are lacking. Synthetic cathinones are beta-ketone amphetamine analogs that have emerged as a heterogeneous class of abused compounds that function as either monoamine transporter substrates or inhibitors.
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