Designer Drugs: N-benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP)

Designer Drugs: N-benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP)

With the influx of designer drugs readily available via Internet sources laboratories across the United States are seeing an increase in cases containing these substances. N-benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl) piperazine (TFMPP) are phenylpiperazine analogues and just two of the numerous compounds available that are often referred to as “designer drugs” or new psychoactive substances. The pharmacological effects of TFMPP include anxiolytic activity, anti-aggressiveness, locomotor inhibition, respiratory depression, interference with circadian system, hypophagia, prevention of isolation-induced behavioral deficit, and rate-depressant effects. BZP has euphoric, stimulant properties with adverse effects of acute psychosis, renal toxicity, and seizures. BZP has a potency of approximately one-tenth that of the drug d-amphetamine [3]. TFMPP and BZP are often sold in combination or alone with street names such as: “Legal X”, “A2”, “legal E”, “Bliss”, “Charge”, “Herbal Ecstasy”, , “Frenzy”, “Nemesis” or the chemical name 1-Benzylpiperazine in the case of BZP. Users of the drug MDMA (3,4-methylenedioxy-N-methylamphetamine) (aka “Ecstasy” or in a powdered or crystalline form “Molly”) either knowingly or unknowing ingest the BZP/TFMPP combination to get the same effects..

These compounds are often used at raves, nightclubs, private parties, and other venues where club drugs are taken or purchased [2]. TFMPP was temporarily placed into schedule I of the Controlled Substances Act [3] on September 20, 2002 (67 FR 59161), however in 2004 the Drug Enforcement Administration (DEA) published a Final Rule (69 FR 12794) in the Federal Register reverting TFMPP to non-control status [2]. BZP was placed in schedule I of the CSA due to high abuse potential and lack of accepted medical use or safety [3].

BZP undergoes ring hydroxylation, n-dealkylation, o-methylation and conjuction metabolism. Research has shown that humans excrete approximately 5% of an oral dose as the parent compound within 24 hours (urine) and there is a similar amount of conjugated metabolites detected [1, 4-6]. Some of the physical changes seen in users of BZP include significantly increased heart rate and systolic blood pressure [7]. In addition to the previously mentioned effects, manifested symptoms include: anxiety, agitation, sweating, hyperventilation, vomiting, dizziness, headache, confusion and collapse. The identification of BZP in ante and postmortem cases is often reported in combination with 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) in addition to TFMPP [8].

TFMPP is a piperazine derivative and serotonin receptor agonist. It is often administered as a hydrochloride salt [1]. It undergoes extensive biotransformation via p-hydroxylation, piperazine ring opening, side-chain oxidation and conjugation. In addition to the parent compound (free and unchanged), it’s metabolites include: conjugated hydroxyl(OH)-TFMPP, N-(3-trifluoromethylphenyl)ehtylenediamine (TFMPED), 3-trifluormethylaniline (TFMA) and the p-hydroxylation products (OH-TFMPED, OH-TFMA) [1, 4]. Users describe the effect of TFMPP as similar to those of MDMA and lysergic acid diethylamide or LSD, and include euphoria, mild central nervous system stimulation and visual distortion in addition to the previously mentioned effects. As with BZP users can experience nausea, vomiting, dizziness, bruxism, mydriasis and tachycardia.

References

[1] (2011) Department of Justice. Drug Enforcement Administration. 1-[3-(Trifluoro-methyl)-phenyl]piperazine)] (Street Names: “TFMPP” or “Molly”. Often found in combination with BZP: “A2”, “Legal E” or “Legal X”). http://www.deadiversion.usdoj.gov/drugs_concern/tfmpp.pdf (Accessed 27 January, 2012)

[2] (2002) Department of Justice. Drug Enforcement Administration. Schedules of Controlled Substances: Temporary Placement of Benzylpiperazine and Trifluoromethylphenylpiperazine Into Schedule I. 21 CFR Part 1308. http://www.deadiversion.usdoj.gov/fed_regs/rules/2002/fr09202.htm (Accessed 27 January, 2012).

[3] R. Baselt (eds) (2011) Disposition of toxic drugs and chemicals in man. Biomedical Publications, Seal Beach, CA, pp. 162-163 and 1740-1741.

[4] R. Staack, G. Fritschi, H. Maurer (2003) Studies on the metabolism and toxicological detection of the new designer drug N-benzylpiperazine in urine using gas chromatography-mass spectrometry. J Mass Spec, 38, 971-981.

[5] H. Tsutsumi, M. Katagi, A. Miki (2005) Isolation, identification and excretion profile of the principal urinary metabolite of the recently banned designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rats. Xenobiotica, 35, 107-116

[6] U. Antia, M. Tingle, B. Russell (2009) In vivo interactions between BZP and TFMPP (party pill drugs). J New Zealand Med Assoc, 122, 29-38.

[7] C. Bye, A. Munro-Faure, A. Peck, P. Young (1973) A comparison of the effects of 1-benzylpiperazine and dexamphetamine on human performance test. Eur. J. Clin. Pharm, 6, 163-169.

[8] M. Baumann, R. Clark, A. Budzynski, J.  Partilla, B. Blough, R. Rothman (2005) N-substituted piperazines abused by humans mimic the molecular mechanisms of 3,4-methylene-dioxymethamphetamien (MDMA, or ‘Ecstasy’). Neuropharm, 30, 550-560.

 

 

 

 

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