Reinforcing effects of abused 'bath salts' constituents 3,4-methylenedioxypyrovalerone and α-pyrrolidinopentiophenone and their enantiomers.
Reinforcing effects of abused 'bath salts' constituents 3,4-methylenedioxypyrovalerone and α-pyrrolidinopentiophenone and their enantiomers.
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DOI：
10.1097/fbp.0000000000000315
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发表时间：
2017-10
影响因子：
1.6
通讯作者：
Collins GT
中科院分区：
文献类型：
--
作者：
Gannon BM;Rice KC;Collins GT
滥用浴盐制剂中发现的合成卡西酮是手性分子。外消旋 3,4-亚甲基二氧基吡咯戊酮 (MDPV) 和 α-吡咯烷五苯酮 (α-PVP) 是这些制剂的两种常见成分，据报道它们是高效的增强剂；然而，每种对映体对这些效应的相对贡献尚未确定。因此，训练雄性 Sprague Dawley 大鼠对外消旋 MDPV 或 α-PVP（每种药物 n=9）做出反应，并在渐进比例强化方案下生成 MDPV 和 α-PVP 的外消旋体以及 S 和 R 对映体的完整剂量反应曲线。 MDPV 和 α-PVP 的外消旋混合物以及每种对映体均以剂量依赖性方式保持响应，其中外消旋 MDPV 和 α-PVP 是等价的。每种药物的效力顺序为 S-对映体 > 外消旋体 >> R-对映体。虽然 α-PVP 的两种对映体与外消旋 α-PVP 一样有效，但 R-MDPV 的增强剂效果略低于 S- 和外消旋 MDPV。这些研究的结果提供了明确的证据，表明 MDPV 和 α-PVP 的两种对映体都是高效增强剂，并且可能导致含有外消旋 MDPV 和/或 α-PVP 的浴盐制剂的滥用相关效应。
Synthetic cathinones found in abused bath salts preparations are chiral molecules. Racemic 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (α-PVP) are two common constituents of these preparations that have been reported to be highly effective reinforcers; however, the relative contribution of each enantiomer to these effects has not been determined. Thus, male Sprague Dawley rats were trained to respond for racemic MDPV or α-PVP (n=9 per drug), with full dose-response curves for the racemate and the S– and R–enantiomers of MDPV and α-PVP generated under a progressive ratio schedule of reinforcement. Racemic mixtures of both MDPV and α-PVP as well as each enantiomer maintained responding in a dose-dependent manner, with racemic MDPV and α-PVP being equipotent. The rank order of potency within each drug was S–enantiomer > racemate >> R–enantiomer. While both enantiomers of α-PVP were as effective as racemic α-PVP, R–MDPV was a slightly less effective reinforcer than both S– and racemic MDPV. The results of these studies provide clear evidence that both enantiomers of MDPV and α-PVP function as highly effective reinforcers and likely contribute to the abuse-related effects of bath salts preparations containing racemic MDPV and/or α-PVP.