title: The clinical toxicology of the designer "party pills" benzylpiperazine and trifluoromethylphenylpiperazine.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Supportive care including the termination of seizures is paramount, with relief of symptoms usually being provided by benzodiazepines alone.
  
  
  CONCLUSIONS
  BZP and TFMP can cause sympathomimetic effects in the intoxicated patient. Appropriate, symptom-directed supportive care should ensure a good recovery.
authors.affiliation: Department of Preventive and Social Medicine, National Poisons Centre, University of Otago, Dunedin, New Zealand. leo.schep@otago.ac.nz
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schep
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Slaughter
authors.forename: J Allister
authors.initials: JA
authors.lastname: Vale
authors.forename: D Michael G
authors.initials: DM
authors.lastname: Beasley
authors.forename: Paul
authors.initials: P
authors.lastname: Gee
mesh_terms: D015198:Designer Drugs / Q000493:pharmacokinetics / Q000633:toxicity*; D005334:Fever / Q000139:chemically induced; D006801:Humans; D013287:Illicit Drugs / Q000493:pharmacokinetics / Q000633:toxicity*; D010879:Piperazines / Q000493:pharmacokinetics / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics / Q000633:toxicity*; D015813:Substance Abuse Detection; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism
chemical_list: D015198:Designer Drugs; D013287:Illicit Drugs; D010879:Piperazines; D017366:Serotonin Receptor Agonists; C018406:1-(3-trifluoromethylphenyl)piperazine; C006737:1-benzylpiperazine