Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, USA.
J Psychopharmacol. 2018 Jul;32(7):802-810. doi: 10.1177/0269881118780613. Epub 2018 Jun 18.
Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit "party pills" or "ecstasy" formulations. Illicit synthesis of BZP often results in production of an impure by-product dibenzylpiperazine (DBZP), which frequently appears alongside BZP in these formulations; however, despite its ubiquity, little information exists regarding the abuse liability of DBZP.
The current study aimed to evaluate the abuse-related behavioral pharmacology of DBZP.
DBZP, mCPP, and TFMPP were tested in parallel in mice in locomotor activity and conditioned place preference assays, and in a drug discrimination assay with rats trained to discriminate either methamphetamine, cocaine, (±)-3,4-methylenedioxymethamphetamine (MDMA), or -2,5-dimethoxy-4-methylamphetamine(DOM).
Each of the compounds tested produced dose-dependent decreases in locomotor activity. DBZP substituted fully for methamphetamine, produced subthreshold drug-appropriate responding for cocaine and MDMA, and failed to substitute for DOM. Conversely, TFMPP and mCPP only produced subthreshold drug-appropriate responding for methamphetamine and MDMA, respectively, and both compounds failed to substitute for cocaine or DOM. None of the compounds tested produced a place preference. DBZP produced convulsions in rats at the highest dose tested.
These data indicate that DBZP is more similar to BZP, albeit with lower potency and efficacy, than its serotonergic piperazine counterparts, and is a behaviorally-active compound with some abuse liability and potential for adverse health effects.
取代哌嗪类化合物构成了新型精神活性物质市场的重要组成部分。在被滥用的哌嗪类化合物中，间氯苯基哌嗪（mCPP）、三氟甲基苯基哌嗪（TFMPP），尤其是苯丙基哌嗪（BZP）被广泛滥用，这些化合物通常单独或组合存在于非法的“派对药丸”或“摇头丸”制剂中。BZP 的非法合成通常会产生不纯的副产品二苄基哌嗪（DBZP），这种物质在这些制剂中经常与 BZP 一起出现；然而，尽管 DBZP 无处不在，但关于其滥用倾向的信息却很少。
本研究旨在评估 DBZP 的与滥用相关的行为药理学特性。
DBZP、mCPP 和 TFMPP 在小鼠的运动活性和条件性位置偏好试验中以及在大鼠药物辨别试验中进行了平行测试，大鼠接受训练以辨别 methamphetamine、可卡因、（±）-3,4-亚甲基二氧基甲 基苯丙胺（MDMA）或 -2,5-二甲氧基-4-甲基苯丙胺（DOM）。
测试的每种化合物都产生了剂量依赖性的运动活性降低。DBZP 完全取代 methamphetamine，产生了 cocaine 和 MDMA 的阈下药物适当反应，并且未能取代 DOM。相反，TFMPP 和 mCPP 仅对 methamphetamine 和 MDMA 产生了阈下药物适当反应，并且这两种化合物均未能取代 cocaine 或 DOM。测试的化合物均未产生位置偏好。DBZP 在最高剂量测试时在大鼠中引起了惊厥。
这些数据表明，DBZP 与其血清素能哌嗪类化合物相比，虽然效力和效价较低，但与 BZP 更相似，是一种具有行为活性的化合物，具有一定的滥用倾向和潜在的健康影响。
