Trifluoromethylphenylpiperazine

Overview

meta-Trifluoromethylphenylpiperazine (TFMPP) is a recreational drug of the phenylpiperazine chemical class and is a substituted piperazine. Usually in combination with benzylpiperazine (BZP) and other analogues, it is sold as an alternative to the illicit drug MDMA ("Ecstasy").[1][2] WP

Uses, dosage and effects

Use and effects

TFMPP is rarely used by itself. In fact, TFMPP reduces locomotor activity and produces aversive effects in animals rather than self-administration, which may explain the decision of the DEA not to permanently make TFMPP a controlled substance. More commonly, TFMPP is co-administered with BZP, which acts as a norepinephrine and dopamine releasing agent. Due to the serotonin agonist effects and increase in serotonin, norepinephrine, and dopamine levels produced by the BZP/TFMPP combination, this mixture of drugs produces effects which crudely mimic those of MDMA.[3][4][5] WP

In clinical studies, TFMPP produced effects in humans including dysphoria, dextroamphetamine-like effects (i.e., stimulant-like effects), tension and anxiety, mental confusion and "bewilderment", and increased ratings of "drug liking", "high", and "stimulated". The drug has been anecdotally reported to produce mild psychedelic effects in humans, but no hallucinogenic effects with the drug were described in clinical studies at the employed dose. The combination of TFMPP with BZP crudely mimics the effects of MDMA in clinical studies.[6][7][8] WP

Risks and side effects

Side effects

The combination of BZP and TFMPP has been associated with a range of side effects, including insomnia, anxiety, nausea and vomiting, headaches and muscle aches which may resemble migraine, seizures, impotence, and rarely psychosis, as well as a prolonged and unpleasant hangover effect. These side effects tend to be significantly worsened when the BZP/TFMPP mix is consumed alongside alcohol, especially the headache, nausea, and hangover.[2] WP

However, it is difficult to say how many of these side effects are produced by TFMPP itself, as it has rarely been marketed without BZP also being present, and all of the side effects mentioned are also produced by BZP (which has been sold as a single drug). Studies into other related piperazine drugs such as mCPP suggest that certain side effects such as anxiety, headache and nausea are common to all drugs of this class, and pills containing TFMPP are reported by users to produce comparatively more severe hangover effects than those containing only BZP. The drug can also cause the body to tremble for a long period of time.[9] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

Pharmacology

Pharmacodynamics

TFMPP has affinity for the 5-HT1A (Kᵢ = 288–1,950 nM), 5-HT1B (Kᵢ = 30–132 nM), 5-HT1D (Kᵢ = 282 nM), 5-HT2A (Kᵢ = 160–269 nM), and 5-HT2C (Kᵢ = 62 nM) receptors, and functions as a full agonist at all sites except the 5-HT2A receptor, where it acts as a weak partial agonist or antagonist. Unlike the related piperazine compound meta-chlorophenylpiperazine (mCPP), TFMPP has insignificant affinity for the 5-HT₃ receptor (IC₅₀ = 2,373 nM). TFMPP also binds to the SERT (EC₅₀ = 121 nM) and evokes the release of serotonin. It has no effects on dopamine or norepinephrine reuptake or efflux.[3][10][11] WP

Findings are mixed on whether TFMPP produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, with some studies finding that it does and others reporting that it does not. In one study, TFMPP did not produce the head-twitch response on its own, but when combined with the selective serotonin 5-HT2C receptor antagonist SB-242084, it was able to dose-dependently induce head twitches. In contrast to the preceding findings, the drug has been found to dose-dependently antagonize the head-twitch response induced by serotonergic psychedelics like DOI. The preceding findings suggest that serotonin 5-HT2C receptor activation inhibits and can mask the head-twitch response induced by serotonin 5-HT2A receptor agonists.[5][12–15] WP

TFMPP has been found to reduce aggression in rodents. TFMPP was not self-administered by rhesus monkeys, suggesting that it lacks reinforcing effects.[16][17][18] WP

Pharmacokinetics

The pharmacokinetics of TFMPP have been studied.[19] WP

History

History

TFMPP was first described in the scientific literature in 1978.[20] WP

Legal status

Canada

Since 2012, TFMPP has been listed as a Schedule III controlled substance in Canada, making possession of TFMPP a federal offence. It has also been added to Part J of the Food and Drug Regulations thereby prohibiting the production, export or import of the substance.[21] WP

China

As of October 2015 TFMPP is a controlled substance in China.[22] WP

Denmark

As of December 3, 2005, TFMPP is illegal in Denmark. WP

Finland

Scheduled in government decree on psychoactive substances banned from the consumer market.[23][24][25] WP

Japan

Since 2003, TFMPP and BZP became illegal in Japan. WP

Netherlands

TFMPP is unscheduled in the Netherlands.[26] WP

New zealand

Based on the recommendation of the EACD, the New Zealand government has passed legislation which placed BZP, along with the other piperazine derivatives TFMPP, mCPP, pFPP, MeOPP and MBZP, into Class C of the New Zealand Misuse of Drugs Act 1975. A ban was intended to come into effect in New Zealand on December 18, 2007, but the law change did not go through until the following year, and the sale of BZP and the other listed piperazines became illegal in New Zealand as of 1 April 2008. An amnesty for possession and usage of these drugs remained until October 2008, at which point they became completely illegal.[27] WP

Sweden

As of March 1, 2006, TFMPP is scheduled as a "dangerous substance" in Sweden.[28] WP

Switzerland

As of December 1, 2010, TFMPP is a controlled substance in Switzerland.[29][30] WP

United kingdom

As of December 2009, TFMPP has been made a Class C drug in the United Kingdom along with BZP. WP

United states

TFMPP is not currently scheduled at the federal level in the United States, but it was briefly emergency scheduled in Schedule I. The scheduling expired in April 2004 and was not renewed. However, some states such as Florida have banned the drug in their criminal statutes making its possession a felony.[31][32][33] WP

Florida

TFMPP is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida.[33] WP

Texas

TFMPP is controlled in Texas under Penalty Group 2, as a hallucinogenic substance. It is illegal to possess TFMPP in any quantity in Texas. WP

Chemistry

Formula

C11H13F3N2 PC

CAS number

15532-75-9 PC

Molar mass (g/mol)

230.23 PC

IUPAC name (computed by PubChem)

1-[3-(trifluoromethyl)phenyl]piperazine PC

SMILES

C1CN(CCN1)C2=CC=CC(=C2)C(F)(F)F PC

InChIKey

KKIMDKMETPPURN-UHFFFAOYSA-N PC

PubChem CID

4296

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Harm reduction site Erowid TFMPP Vault: Basics
2. Journal / agency Schep LJ, Slaughter RJ, Vale JA, Beasley DM, Gee P. The clinical toxicology of the designer "party pills" benzylpiperazine and trifluoromethylphenylpiperazine. Clinical Toxicology. March 2011. doi:10.3109/15563650.2011.572076 · PMID 21495881
3. Journal / agency Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB. N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy'). Neuropsychopharmacology. March 2005. doi:10.1038/sj.npp.1300585 · PMID 15496938
4. Journal / agency Partilla JS, Dempsey AG, Nagpal AS, Blough BE, Baumann MH, Rothman RB. Interaction of amphetamines and related compounds at the vesicular monoamine transporter. The Journal of Pharmacology and Experimental Therapeutics. October 2006. doi:10.1124/jpet.106.103622 · PMID 16835371
5. Journal / agency Yarosh HL, Katz EB, Coop A, Fantegrossi WE. MDMA-like behavioral effects of N-substituted piperazines in the mouse. Pharmacology, Biochemistry, and Behavior. November 2007. doi:10.1016/j.pbb.2007.06.007 · PMID 17651790 · PMC2082056
6. Journal / agency Jan RK, Lin JC, Lee H, Sheridan JL, Kydd RR, Kirk IJ, Russell BR. Determining the subjective effects of TFMPP in human males. Psychopharmacology. August 2010. doi:10.1007/s00213-010-1911-y · PMID 20552171
7. Journal / agency Lin JC, Jan RK, Kydd RR, Russell BR. Subjective effects in humans following administration of party pill drugs BZP and TFMPP alone and in combination. Drug Testing and Analysis. September 2011. doi:10.1002/dta.285 · PMID 21538945
8. Journal / agency Lin JC, Jan RK, Lee H, Jensen MA, Kydd RR, Russell BR. Determining the subjective and physiological effects of BZP combined with TFMPP in human males. Psychopharmacology. April 2011. doi:10.1007/s00213-010-2081-7 · PMID 21060995
9. Other Wilkins C, Girling M, Sweetsur P, Huckle T, Huakau J. Legal party pill use in New Zealand: Prevalence of use, availability, health harms and 'gateway effects' of benzylpiperazine (BZP) and trifluorophenylmethylpiperazine (TFMPP)
10. Journal / agency Glennon RA. Central serotonin receptors as targets for drug research. Journal of Medicinal Chemistry. January 1987. doi:10.1021/jm00384a001 · PMID 3543362
11. Journal / agency Robertson DW, Bloomquist W, Wong DT, Cohen ML. mCPP but not TFMPP is an antagonist at cardiac 5HT3 receptors. Life Sciences. 1992. doi:10.1016/0024-3205(92)90372-V · PMID 1736030
12. Journal / agency Vickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, Kennett GA. Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists. Pharmacology, Biochemistry, and Behavior. 2001. doi:10.1016/s0091-3057(01)00552-4 · PMID 11509227
13. Journal / agency Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ. (1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists. The Journal of Pharmacology and Experimental Therapeutics. April 1995. doi:10.1016/S0022-3565(25)09485-6 · PMID 7714755
14. Journal / agency Simansky KJ, Schechter LE. Properties of some 1-arylpiperazines as antagonists of stereotyped behaviors mediated by central serotonergic receptors in rodents. The Journal of Pharmacology and Experimental Therapeutics. December 1988. doi:10.1016/S0022-3565(25)13260-6 · PMID 3144595
15. Journal / agency Berendsen HH, Broekkamp CL. Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice. British Journal of Pharmacology. November 1990. doi:10.1111/j.1476-5381.1990.tb14138.x · PMID 2150180 · PMC1917735
16. Journal / agency Olivier B, Mos J, van Oorschot R, Hen R. Serotonin receptors and animal models of aggressive behavior. Pharmacopsychiatry. October 1995. doi:10.1055/s-2007-979624 · PMID 8614705
17. Journal / agency Muehlenkamp F, Lucion A, Vogel WH. Effects of selective serotonergic agonists on aggressive behavior in rats. Pharmacology, Biochemistry, and Behavior. April 1995. doi:10.1016/0091-3057(95)00351-7 · PMID 7617717
18. Journal / agency Fantegrossi WE, Winger G, Woods JH, Woolverton WL, Coop A. Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys. Drug and Alcohol Dependence. February 2005. doi:10.1016/j.drugalcdep.2004.07.014 · PMID 15664717
19. Journal / agency Antia U, Tingle MD, Russell BR. Validation of an LC-MS method for the detection and quantification of BZP and TFMPP and their hydroxylated metabolites in human plasma and its application to the pharmacokinetic study of TFMPP in humans. Journal of Forensic Sciences. September 2010. doi:10.1111/j.1556-4029.2010.01457.x · PMID 20533987
20. Journal / agency Fuller RW, Snoddy HD, Mason NR, Molloy BR. Effect of 1-(m-trifluoromethylphenyl)-piperazine on 3H-serotonin binding to membranes from rat brain in vitro and on serotonin turnover in rat brain in vivo. European Journal of Pharmacology. November 1978. doi:10.1016/0014-2999(78)90016-x · PMID 720384
21. Other SOR/2012-65 March 30, 2012 Controlled Drugs and Substances Act
22. Journal / agency 关于印发《非药用类麻醉药品和精神药品列管办法》的通知. 27 September 2015
23. Other FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 1129/2015
24. Other FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 225/2017
25. Other FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 733/2021
26. Other Weed A. Trifluoromethylphenylpiperazine. 2023-10-18
27. Other Misuse of Drugs (Classification of BZP) Amendment Bill 2008
28. Harm reduction site Erowid TFMPP Vault: Legal Status
29. Other RO 2010 4099
30. Other RO 2011 2595
31. Other §1308.11 Schedule I
32. Other Scheduling Actions 2002
33. Other Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL

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