Trifluoromethylphenylpiperazine

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.{{cite journal |vauthors=Partilla JS, Dempsey AG, Nagpal AS, Blough BE, Baumann MH, Rothman RB |title=Interaction of amphetamines and related compounds at the vesicular monoamine transporter |journal=Journal of Pharmacology and Experimental Therapeutics |date=October 2006 |volume=319 |issue=1 |pages=237–46 |doi=10.1124/jpet.106.103622 |pmid=16835371|citeseerx=10.1.1.690.6669 |s2cid=22730478 }} 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.{{cite journal |vauthors=Yarosh HL, Katz EB, Coop A, Fantegrossi WE |title=MDMA-like behavioral effects of N-substituted piperazines in the mouse |journal=Pharmacology Biochemistry and Behavior |date=November 2007 |volume=88 |issue=1 |pages=18–27 |doi=10.1016/j.pbb.2007.06.007|pmid=17651790 |pmc=2082056 }}

In a clinical study, 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".{{cite journal | vauthors = Jan RK, Lin JC, Lee H, Sheridan JL, Kydd RR, Kirk IJ, Russell BR | title = Determining the subjective effects of TFMPP in human males | journal = Psychopharmacology (Berl) | volume = 211 | issue = 3 | pages = 347–353 | date = August 2010 | pmid = 20552171 | doi = 10.1007/s00213-010-1911-y | url = }} The drug has been anecdotally reported to produce mild psychedelic effects in humans, but no hallucinogenic effects with the drug were described in the study at the employed dose.

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.

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.{{cite web | vauthors =Wilkins C, Girling M, Sweetsur P, Huckle T, Huakau J | title =Legal party pill use in New Zealand: Prevalence of use, availability, health harms and 'gateway effects' of benzylpiperazine (BZP) and trifluorophenylmethylpiperazine (TFMPP) | publisher =Centre for Social and Health Outcomes Research and Evaluation (SHORE) | url =http://www.spiritualhigh.co.uk/spiritualhigh.co.uk/downloads/Legal-party-pills-in-New-Zealand-report.pdf | access-date =2007-04-14 | url-status =dead | archive-url =https://web.archive.org/web/20070318042503/http://www.spiritualhigh.co.uk/spiritualhigh.co.uk/downloads/Legal-party-pills-in-New-Zealand-report.pdf | archive-date =2007-03-18 }}{{unreliable source?|date=February 2015}}

TFMPP has affinity for the 5-HT_1A (K_i = 288 nM), 5-HT_1B (K_i = 132 nM), 5-HT_1D (K_i = 282 nM), 5-HT_2A (K_i = 269 nM), and 5-HT_2C (K_i = 62 nM) receptors, and functions as a full agonist at all sites except the 5-HT_2A receptor, where it acts as a weak partial agonist or antagonist.{{cite journal |vauthors=Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB | title = N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') | journal = Neuropsychopharmacology | volume = 30 | issue = 3 | pages = 550–60 |date=March 2005 | pmid = 15496938 | doi = 10.1038/sj.npp.1300585 | s2cid = 24217984 | doi-access = free }} Unlike the related piperazine compound meta-chlorophenylpiperazine (mCPP), TFMPP has insignificant affinity for the 5-HT₃ receptor (IC₅₀ = 2,373 nM).{{cite journal |vauthors=Robertson DW, Bloomquist W, Wong DT, Cohen ML | title = mCPP but not TFMPP is an antagonist at cardiac 5HT3 receptors | journal = Life Sciences | volume = 50 | issue = 8 | pages = 599–605 | year = 1992 | pmid = 1736030 | doi = 10.1016/0024-3205(92)90372-V}} 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.

TFMPP has been found to reduce aggression in rodents.{{cite journal | vauthors = Olivier B, Mos J, van Oorschot R, Hen R | title = Serotonin receptors and animal models of aggressive behavior | journal = Pharmacopsychiatry | volume = 28 Suppl 2 | issue = | pages = 80–90 | date = October 1995 | pmid = 8614705 | doi = 10.1055/s-2007-979624 | url = }}{{cite journal | vauthors = Muehlenkamp F, Lucion A, Vogel WH | title = Effects of selective serotonergic agonists on aggressive behavior in rats | journal = Pharmacol Biochem Behav | volume = 50 | issue = 4 | pages = 671–674 | date = April 1995 | pmid = 7617717 | doi = 10.1016/0091-3057(95)00351-7 | url = }} It produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and hence would be predicted to have hallucinogenic effects in humans.{{cite journal | vauthors = Yarosh HL, Katz EB, Coop A, Fantegrossi WE | title = MDMA-like behavioral effects of N-substituted piperazines in the mouse | journal = Pharmacol Biochem Behav | volume = 88 | issue = 1 | pages = 18–27 | date = November 2007 | pmid = 17651790 | pmc = 2082056 | doi = 10.1016/j.pbb.2007.06.007 | url = }}{{cite journal | vauthors = Vickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, Kennett GA | title = Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists | journal = Pharmacol Biochem Behav | volume = 69 | issue = 3-4 | pages = 643–652 | date = 2001 | pmid = 11509227 | doi = 10.1016/s0091-3057(01)00552-4 | url = }} TFMPP was not self-administered by rhesus monkeys, suggesting that it lacks reinforcing effects.{{cite journal | vauthors = Fantegrossi WE, Winger G, Woods JH, Woolverton WL, Coop A | title = Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys | journal = Drug Alcohol Depend | volume = 77 | issue = 2 | pages = 161–168 | date = February 2005 | pmid = 15664717 | doi = 10.1016/j.drugalcdep.2004.07.014 | url = }}

Since 2012, TFMPP has been listed as a Schedule III controlled substance in Canada,{{cite web|title=SOR/2012-65 March 30, 2012 Controlled Drugs and Substances Act|url=http://gazette.gc.ca/rp-pr/p2/2012/2012-04-11/html/sor-dors65-eng.html#archived|website=Canada Gazette|publisher=Government of Canada|access-date=15 September 2014}} 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.

As of October 2015 TFMPP is a controlled substance in China.{{cite web | url=http://www.sfda.gov.cn/WS01/CL0056/130753.html | title=关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | publisher=China Food and Drug Administration | date=27 September 2015 | language=zh | access-date=1 October 2015}}

Scheduled in government decree on psychoactive substances banned from the consumer market.{{cite web | url=https://www.finlex.fi/fi/laki/alkup/2015/20151129 | title=FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 1129/2015 }}{{cite web | url=https://www.finlex.fi/fi/laki/alkup/2017/20170225 | title=FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 225/2017 }}{{cite web | url=https://www.finlex.fi/fi/laki/alkup/2021/20210733 | title=FINLEX ® - Säädökset alkuperäisinä: Valtioneuvoston asetus kuluttajamarkkinoilta… 733/2021 }}

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

Since 2003, TFMPP and BZP became illegal in Japan.

TFMPP is unscheduled in the Netherlands. {{Citation needed|date=April 2023}}

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.{{cite web |url=http://www.parliament.nz/en-NZ/PB/Legislation/Bills/d/3/d/00DBHOH_BILL8220_1-Misuse-of-Drugs-Classification-of-BZP-Amendment.htm |title=Misuse of Drugs (Classification of BZP) Amendment Bill 2008}}

As of March 1, 2006, TFMPP is scheduled as a "dangerous substance" in Sweden.{{cite web |url=https://www.erowid.org/chemicals/tfmpp/tfmpp_law.shtml |title=Erowid TFMPP Vault : Legal Status |publisher=Erowid}}

As of December 1, 2010, TFMPP is a controlled substance in Switzerland.{{cite web |title=RO 2010 4099 |url=https://fedlex.data.admin.ch/eli/oc/2010/599 |publisher=Fedlex |access-date=2022-08-16}}{{cite web | url=https://www.fedlex.admin.ch/eli/cc/2011/363/fr| title=RO 2011 2595 |publisher=Fedlex |access-date=2022-08-16}}

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

TFMPP is not currently scheduled at the federal level in the United States,{{Cite web |url=http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm |title=§1308.11 Schedule I. |access-date=2014-12-17 |archive-date=2009-08-27 |archive-url=https://web.archive.org/web/20090827043725/http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm |url-status=dead }} but it was briefly emergency scheduled in Schedule I. The scheduling expired in April 2004 and was not renewed.{{cite web |url=http://www.deadiversion.usdoj.gov/fed_regs/sched_actions/2002/fr09202.htm |title=Scheduling Actions 2002 |publisher=U.S. Department of Justice, Drug Enforcement Administration (DEA) |url-status=dead |archive-url=https://web.archive.org/web/20030102043925/http://www.deadiversion.usdoj.gov/fed_regs/sched_actions/2002/fr09202.htm |archive-date=2003-01-02 }} However, some states such as Florida have banned the drug in their criminal statutes making its possession a felony.[http://leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0800-0899/0893/0893.html Florida Statutes - Chapter 893 - DRUG ABUSE PREVENTION AND CONTROL]

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

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

• Antrafenine
• CPD-1

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• [//www.erowid.org/chemicals/tfmpp/tfmpp.shtml Erowid: TFMPP Vault]

{{Entactogens}}

{{Psychedelics}}

{{Serotonin receptor modulators}}

{{Monoamine releasing agents}}

{{Piperazines}}

Category:5-HT1A agonists

Category:5-HT1B agonists

Category:5-HT1D agonists

Category:5-HT2A agonists

Category:5-HT2C agonists

Category:Designer drugs

Category:1-Piperazinyl compounds

Category:Psychedelic arylpiperazines

Category:Serotonin receptor agonists

Category:Serotonin releasing agents