Department of Preventive and Social Medicine, National Poisons Centre, University of Otago, Dunedin, New Zealand.
Clin Toxicol (Phila). 2011 Mar;49(3):131-41. doi: 10.3109/15563650.2011.572076.
Benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) are synthetic phenylpiperazine analogues. BZP was investigated as a potential antidepressant in the early 1970s but was found unsuitable for this purpose. More recently, BZP and TFMPP have been used as substitutes for amfetamine-derived designer drugs. They were legally available in a number of countries, particularly in New Zealand, and were marketed as party pills, but are now more heavily regulated. This article will review the mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management of poisoning due to BZP and TFMPP.
OVID MEDLINE and ISI Web of Science were searched systematically for studies on BZP and TFMPP and the bibliographies of identified articles were screened for additional relevant studies including nonindexed reports. Nonpeer-reviewed sources were also accessed. In all, 179 papers excluding duplicates were identified and 74 were considered relevant.
BZP and TFMPP have stimulant and amfetamine-like properties. They enhance the release of catecholamines, particularly of dopamine, from sympathetic nerve terminals, increasing intra-synaptic concentrations. The resulting elevated intra-synaptic monoamine concentrations cause increased activation of both central and peripheral α- and β-adrenergic postsynaptic receptors. BZP has primarily dopaminergic and noradrenergic action while TFMPP has a more direct serotonin agonist activity.
There is limited information on the kinetics of these drugs. Following ingestion, peak plasma concentrations are reached after 60 to 90 min. Both drugs would be expected to cross the blood brain barrier and they are metabolized mainly by hydroxylation and N-dealkylation catalyzed by cytochrome P450 and catechol-o-methyl transferase enzymes. In humans, only small amounts of both BZP and TFMPP are excreted in the urine, suggesting a low bioavailability. The serum half-lives of BZP and TFMPP are relatively short with elimination being essentially complete in 44 h for BZP and 24 h for TFMPP.
These compounds can cause harmful effects when taken recreationally. Commonly reported features include palpitations, agitation, anxiety, confusion, dizziness, headache, tremor, mydriasis, insomnia, urine retention, and vomiting. Seizures are induced in some patients even at low doses. Severe multiorgan toxicity has been reported, though fatalities have not been recorded conclusively.
Supportive care including the termination of seizures is paramount, with relief of symptoms usually being provided by benzodiazepines alone.
BZP and TFMP can cause sympathomimetic effects in the intoxicated patient. Appropriate, symptom-directed supportive care should ensure a good recovery.
苯丙哌嗪（BZP）和三氟甲基苯丙哌嗪（TFMPP）是合成苯丙哌嗪类似物。BZP 在 20 世纪 70 年代早期被研究为一种潜在的抗抑郁药，但被发现不适合用于此目的。最近，BZP 和 TFMPP 已被用作苯丙胺类设计药物的替代品。它们在许多国家，特别是在新西兰，都是合法供应的，并作为派对药丸出售，但现在受到更严格的监管。本文将回顾 BZP 和 TFMPP 中毒的毒性机制、毒代动力学、临床特征、诊断和管理。
系统地在 OVID MEDLINE 和 ISI Web of Science 上搜索关于 BZP 和 TFMPP 的研究，并对确定的文章的参考文献进行筛选，以寻找其他相关研究，包括未索引的报告。还查阅了非同行评审的资料。总共排除重复项后确定了 179 篇论文，其中 74 篇被认为是相关的。
BZP 和 TFMPP 具有兴奋剂和苯丙胺样的特性。它们增强了去甲肾上腺素能神经末梢儿茶酚胺的释放，特别是多巴胺，增加了突触内浓度。由此产生的升高的突触内单胺浓度导致中枢和外周α-和β-肾上腺素能突触后受体的过度激活。BZP 主要具有多巴胺能和去甲肾上腺素能作用，而 TFMPP 具有更直接的血清素激动剂活性。
关于这些药物的动力学信息有限。摄入后，60 至 90 分钟达到血浆峰浓度。预计这两种药物都会穿过血脑屏障，它们主要通过细胞色素 P450 和儿茶酚-O-甲基转移酶酶催化的羟化和 N-脱烷基化代谢。在人类中，只有少量的 BZP 和 TFMPP 被排泄在尿液中，这表明生物利用度较低。BZP 和 TFMPP 的血清半衰期相对较短，BZP 基本上在 44 小时内完全消除，TFMPP 在 24 小时内完全消除。
这些化合物在娱乐性使用时会造成有害影响。常报告的特征包括心悸、激动、焦虑、意识混乱、头晕、头痛、震颤、瞳孔散大、失眠、尿潴留和呕吐。一些患者即使服用低剂量也会引发癫痫发作。已报道严重的多器官毒性，但尚未明确记录到致命病例。
包括终止癫痫发作在内的支持性护理至关重要，苯二氮䓬类药物通常可以单独缓解症状。
BZP 和 TFMPP 可在中毒患者中引起拟交感神经作用。适当的、对症支持性护理应确保良好的恢复。
