1. Introduction

1. The identification of two designer drugs, 1-benzylpiperazine (BZP) and 1-(3-chlorophenyl)piperazine (mCPP): implications for usersMario Mifsud, Dr. Kim Wolff, Dr. Sue Jickells and Dr. Janet MifsudInstitute of Psychiatry, King’s College London, University of East Anglia and University of Malta. 1. Introduction • Designer drugs containing the piperazine moiety, such as the 1-aryl-piperazine compounds, are known to be psychoactive in man [1]. • One such drug BZP is usually consumed orally, although smoking and snorting have also been reported at rave parties [2]. • Another piperazine compound mCPP is mostly sold in tablet form as “ecstasy” and is used in a similar pattern [3]. • On two separate occasions, the Malta Forensic Laboratory has received 2 seizures of white tablets for analyses. 2. Methods • Two seizures: • Seizure 1 consisted of 69 diamond shaped (sample 1a) and 100 round shaped tablets (sample 1b), both without logo, • and Seizure 2 consisted of 50,579 tablets with a crocodile logo (sample 2). • The following analyses were conducted on the samples taken from the tablets: • Colour tests and Thin layer chromatography (TLC); • Gas chromatography-mass spectrometry (GC-MS) (EI) of organic extracts from alkaline aqueous solutions of the tablets; • Nuclear Magnetic Resonance (1HMR) of tablets from sample 2; • and Friability and Uniformity of content of the tablets. 3. Results and Discussion • Samples 1a and 1b gave a positive colourimetric test (blue colour) result with Simon’s Reagent while sample 2 showed no colouration. • TLC identified compounds for the three samples; • Samples 1a and 1b gave a similar peak with a retention time of 5.96 min and sample 2 a peak with retention time 10.30 min. • The tablets were not found to contain any 3,4-methylenedioxymethamphetamine MDMA. • The mass spectrum of the compound from samples 1a and 1b had a base peak of m/z 91 with ions at m/z 134, 56, 176, 65, and 85 and matched a reference sample for BZP, • The mass spectrum of the compound from sample 2 had a base peak of m/z 154 with ions at m/z 196, 156, 56, 138, and 111 and matched a reference sample for mCPP. • The presence of mCPP isomer was confirmed by IHNMR analyses. • All tablets appeared to be well made and their active drug content and purity was indicative of an organized common production process. • Tablets containing BZP and mCPP • Knowledge of the pharmacokinetics of BZP is still scant; • It appears that peak physiological and subjective effects of both BZP and mCPP are felt about 2 hours after ingestion, [4, 5]. • Side effects of BZP vary from tachycardia and hypertension, [2] to agitation and hyperactivity [6]. • mCPP elicits large increases in the synaptic concentrations of serotonin (5-HT) [3] but the effects on the dopamine system are less pronounced.[7] • mCPP appears to be involved in the control of adrenocorticotropic hormone (ACTH), cortisol and prolactin and is reported to increase cerebral metabolism of glucose [8]. • Adverse effects of mCPP include panic attacks, anorexia, increased body temperature, anxiety, dizziness, shivering, heightened sensitivity to light and noise, fear of losing control [3]. • Fatalities have not been reported with BZP or mCPP alone [3, 9]. 4. Conclusion • While users should be aware that seeking ‘ecstasy effect’ from tablets containing BZP and mCPP runs the same risks as taking MDMA, those in emergency medicine should recognise the relationship of designer drugs such as BZP and mCPP to adverse events more traditionally associated with MDMA. References • De Boer D, Bosman IJ, Hidvegi E, Manzoni C, Benko AA, Dos Reys LJAL, Maes RAA. Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market, J. Forensic Sci. Int. 2001; 121:47-56. • US Department of Justice, National Drug Intelligence Centre. BZP fast facts – Questions and Answers. http://www.usdoj.gov/ndic/pubs11/ 11052/index.htm 2004 (accessed 23 Nov 2007). • EMCDDA Active Monitoring Report on a new psychoactive substance: 1-(3-chlorophenyl)piperazine (mCPP), 2007c. http://www.emcdda.europa.eu/index. cfm? fuseaction =public (accessed 12 Aug 2007). • EMCDDA, Sedefor R.,Report on the risk assessment of BZP in the framework of the Council decision on new psychoactive substances. 2009; published, Lisbon Portugal. • EMCDDA BZP and other piperazines. http://www.emcdda.europa.eu/publications/drug-profiles/bzp (accessed: 12 Jan 2010). • Tekas K, Tothfalusi L, Malomvolgyi B, et al. Studies on the biochemical mode of action of EGYT-475, a new antidepressant, Pol. J. Pharmacol. Pharm. (Engl.abstract) 39 1987; 39:203-11. • Gobbi M, Moia M, Pirona L, et al. p-Methylthioamphetamine and 1-(m-chlorophenyl)piperazine, two non-neurotoxic 5-HT releasers in vivo, differ from neurotoxic amphetamine derivatives in their mode of action at 5-HT nerve endings in vitro.J. Neurochem. 2002; 82:1435-43. • Hommer D, Andreasen P, Rio D, et al.Effects of m-chlorophenylpiperazine on regional brain glucose utilization: A positron emission tomographic comparison of alcoholic and control subjects, J. Neurosci. 1997; 17:2796-2806. • The Expert Advisory Committee on Drugs (EACD) Advice to the Minister On: Benzylpiperazine (BZP), 2004.