Gatch Michael B, Dolan Sean B, Forster Michael J
Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas
Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas.
J Pharmacol Exp Ther. 2015 Aug;354(2):103-10. doi: 10.1124/jpet.115.223586. Epub 2015 May 21.
Synthetic cathinones, often sold as "bath salts," are a popular class of recreational drugs used as quasi-legal alternatives to cocaine, methamphetamine, and methylenedioxymethamphetamine. The increased prevalence and health consequences of synthetic cathinone use has prompted regulatory agencies to control a number of these compounds; however, a broad class of analogous compounds known as the second-generation cathinones has been brought to the market to take the place of the banned synthetic cathinone derivatives. The current study aims to characterize the behavioral pharmacology of three pyrrolidinylated second-generation cathinones: 4-methyl-α-pyrrolidinopropiophenone (4'-MePPP), α-pyrrolidinopropiobutiophenone (α-PBP), and α-pyrrolidinopentiophenone (α-PVP). Locomotor activity was tested in mice over an 8-hour period. The discriminative stimulus effects of these compounds were tested in rats trained to discriminate either cocaine or methamphetamine. The rewarding effects of these drugs were assessed in mice using conditioned place preference. Both α-PBP and α-PVP produced long-lasting increases in locomotor activity across a wide range of doses, whereas 4'-MePPP produced locomotor stimulation only at 30 mg/kg. Both α-PBP and α-PVP fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine, whereas 4'-MePPP substituted fully for the discriminative stimulus effects of methamphetamine only. Both α-PBP and α-PVP produced conditioned place preference in an inverted U-shaped dose effect, whereas 4'-MePPP did not produce conditioned place preference. These findings suggest that α-PBP and α-PVP are likely to be recreationally used and have potential for addiction and abuse, but 4'-MePPP may not.
合成卡西酮，通常作为“浴盐”出售，是一类广受欢迎的消遣性药物，用作可卡因、甲基苯丙胺和亚甲基二氧甲基苯丙胺的准合法替代品。合成卡西酮使用的增加及其对健康的影响促使监管机构对其中一些化合物进行管控；然而，一类被称为第二代卡西酮的类似化合物已投放市场以取代被禁的合成卡西酮衍生物。本研究旨在表征三种吡咯烷基化第二代卡西酮的行为药理学特性：4-甲基-α-吡咯烷基苯丙酮（4'-MePPP）、α-吡咯烷基苯丁酮（α-PBP）和α-吡咯烷基戊酮（α-PVP）。在小鼠身上进行了为期8小时的运动活性测试。在经过训练以区分可卡因或甲基苯丙胺的大鼠身上测试了这些化合物的辨别刺激效应。使用条件性位置偏爱在小鼠身上评估了这些药物的奖赏效应。α-PBP和α-PVP在很宽的剂量范围内都能使运动活性产生持久增加，而4'-MePPP仅在30mg/kg时产生运动兴奋作用。α-PBP和α-PVP都能完全替代可卡因和甲基苯丙胺的辨别刺激效应，而4'-MePPP仅能完全替代甲基苯丙胺的辨别刺激效应。α-PBP和α-PVP都以倒U形剂量效应产生条件性位置偏爱，而4'-MePPP未产生条件性位置偏爱。这些发现表明，α-PBP和α-PVP可能会被用于消遣，并有成瘾和滥用的可能性，但4'-MePPP可能不会。
