Meta-Chlorophenylpiperazine

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 457790176

| drug_name = meta-Chlorophenylpiperazine

| IUPAC_name = 1-(3-chlorophenyl)piperazine

| image = MCPP.svg

| width = 185px

| image2 = MCPP-3D-vdW.png

| width2 = 165px

| tradename =

| legal_AU =

| legal_BR = F2

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-07-25}}

| legal_CA =

| legal_DE = Anlage II

| legal_NZ =

| legal_UK =

| legal_US =

| legal_UN =

| legal_EU =

| routes_of_administration = Oral, intranasal, rectal

| bioavailability =

| metabolism = Liver (CYP2D6)

| elimination_half-life = 4–14 hours{{cite journal | vauthors = Rotzinger S, Bourin M, Akimoto Y, Coutts RT, Baker GB | title = Metabolism of some "second"- and "fourth"-generation antidepressants: iprindole, viloxazine, bupropion, mianserin, maprotiline, trazodone, nefazodone, and venlafaxine | journal = Cellular and Molecular Neurobiology | volume = 19 | issue = 4 | pages = 427–442 | date = August 1999 | pmid = 10379419 | doi = 10.1023/a:1006953923305 | s2cid = 19585113 | pmc = 11545446 }}{{cite book|vauthors = Schatzberg AF,Nemeroff CB|title=The American Psychiatric Association Publishing Textbook of Psychopharmacology, Fifth Edition|url=https://books.google.com/books?id=KfHEDgAAQBAJ&pg=PA460|year=2017|publisher=American Psychiatric Pub|isbn=978-1-58562-523-9|pages=460–}}

| excretion = Urine

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 6640-24-0

| ATC_prefix = N06

| ATC_suffix =

| PubChem = 1355

| IUPHAR_ligand = 142

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 1314

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = REY0CNO998

| KEGG = C11738

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 10588

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 478

| C=10 | H=13 | Cl=1 | N=2

| SMILES = Clc1cc(ccc1)N2CCNCC2

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C10H13ClN2/c11-9-2-1-3-10(8-9)13-6-4-12-5-7-13/h1-3,8,12H,4-7H2

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = VHFVKMTVMIZMIK-UHFFFAOYSA-N

}}

meta-Chlorophenylpiperazine (mCPP) is a psychoactive drug of the phenylpiperazine class. It was initially developed in the late-1970s and used in scientific research before being sold as a designer drug in the mid-2000s.{{cite journal | vauthors = Bossong MG, Van Dijk JP, Niesink RJ | title = Methylone and mCPP, two new drugs of abuse? | journal = Addiction Biology | volume = 10 | issue = 4 | pages = 321–323 | date = December 2005 | pmid = 16318952 | doi = 10.1080/13556210500350794 | url = http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1355-6215&date=2005&volume=10&issue=4&spage=321 | url-status = dead | s2cid = 36169592 | archive-url = https://archive.today/20130105180901/http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1355-6215&date=2005&volume=10&issue=4&spage=321 | archive-date = 2013-01-05 | url-access = subscription }}{{cite journal | vauthors = Lecompte Y, Evrard I, Arditti J | title = [Metachlorophenylpiperazine (mCPP): a new designer drug] | language = fr | journal = Therapie | volume = 61 | issue = 6 | pages = 523–530 | year = 2006 | pmid = 17348609 | doi = 10.2515/therapie:2006093 }} It has been detected in pills touted as legal alternatives to illicit stimulants in New Zealand and pills sold as "ecstasy" in Europe and the United States.{{cite journal | vauthors = Bossong MG, Brunt TM, Van Dijk JP, Rigter SM, Hoek J, Goldschmidt HM, Niesink RJ | title = mCPP: an undesired addition to the ecstasy market | journal = Journal of Psychopharmacology | volume = 24 | issue = 9 | pages = 1395–1401 | date = September 2010 | pmid = 19304863 | doi = 10.1177/0269881109102541 | s2cid = 11186375 }}{{cite journal | vauthors = Vogels N, Brunt TM, Rigter S, van Dijk P, Vervaeke H, Niesink RJ | title = Content of ecstasy in the Netherlands: 1993-2008 | journal = Addiction | volume = 104 | issue = 12 | pages = 2057–2066 | date = December 2009 | pmid = 19804461 | doi = 10.1111/j.1360-0443.2009.02707.x | doi-access = free }}

Despite its advertisement as a recreational substance, mCPP is actually generally considered to be an unpleasant experience and is not desired by drug users. It lacks any reinforcing effects, but has "psychostimulant, anxiety-provoking, and hallucinogenic effects."{{Cite web|last=World Health Organization|date=|title=1-(3-chlorophenyl) piperazine (mCPP) - Expert peer review on pre-review report|url=http://158.232.12.119/entity/medicines/areas/quality_safety/5.3cmCPPpre-review.pdf|archive-url=|archive-date=|access-date=2021-01-12|website=}}{{cite journal | vauthors = Tancer ME, Johanson CE | title = The subjective effects of MDMA and mCPP in moderate MDMA users | journal = Drug and Alcohol Dependence | volume = 65 | issue = 1 | pages = 97–101 | date = December 2001 | pmid = 11714594 | doi = 10.1016/s0376-8716(01)00146-6 }}{{cite journal | vauthors = Tancer M, Johanson CE | title = Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP | journal = Drug and Alcohol Dependence | volume = 72 | issue = 1 | pages = 33–44 | date = October 2003 | pmid = 14563541 | doi = 10.1016/S0376-8716(03)00172-8 }} It is also known to produce dysphoric, depressive, and anxiogenic effects in rodents and humans,{{cite journal | vauthors = Rajkumar R, Pandey DK, Mahesh R, Radha R | title = 1-(m-Chlorophenyl)piperazine induces depressogenic-like behaviour in rodents by stimulating the neuronal 5-HT(2A) receptors: proposal of a modified rodent antidepressant assay | journal = European Journal of Pharmacology | volume = 608 | issue = 1–3 | pages = 32–41 | date = April 2009 | pmid = 19269287 | doi = 10.1016/j.ejphar.2009.02.041 }}{{cite journal | vauthors = Kennett GA, Whitton P, Shah K, Curzon G | title = Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists | journal = European Journal of Pharmacology | volume = 164 | issue = 3 | pages = 445–454 | date = May 1989 | pmid = 2767117 | doi = 10.1016/0014-2999(89)90252-5 }} and can induce panic attacks in individuals susceptible to them.{{cite journal | vauthors = Klein E, Zohar J, Geraci MF, Murphy DL, Uhde TW | title = Anxiogenic effects of m-CPP in patients with panic disorder: comparison to caffeine's anxiogenic effects | journal = Biological Psychiatry | volume = 30 | issue = 10 | pages = 973–984 | date = November 1991 | pmid = 1756202 | doi = 10.1016/0006-3223(91)90119-7 | s2cid = 43010184 | url = https://zenodo.org/record/1253832 }}{{cite journal | vauthors = Charney DS, Woods SW, Goodman WK, Heninger GR | title = Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects | journal = Psychopharmacology | volume = 92 | issue = 1 | pages = 14–24 | year = 1987 | pmid = 3110824 | doi = 10.1007/bf00215473 | s2cid = 43079787 }}{{cite journal | vauthors = Van Veen JF, Van der Wee NJ, Fiselier J, Van Vliet IM, Westenberg HG | title = Behavioural effects of rapid intravenous administration of meta-chlorophenylpiperazine (m-CPP) in patients with generalized social anxiety disorder, panic disorder and healthy controls | journal = European Neuropsychopharmacology | volume = 17 | issue = 10 | pages = 637–642 | date = October 2007 | pmid = 17481859 | doi = 10.1016/j.euroneuro.2007.03.005 | s2cid = 41601926 }}{{cite journal | vauthors = van der Wee NJ, Fiselier J, van Megen HJ, Westenberg HG | title = Behavioural effects of rapid intravenous administration of meta-chlorophenylpiperazine in patients with panic disorder and controls | journal = European Neuropsychopharmacology | volume = 14 | issue = 5 | pages = 413–417 | date = October 2004 | pmid = 15336303 | doi = 10.1016/j.euroneuro.2004.01.001 | s2cid = 28987431 }} It also worsens obsessive–compulsive symptoms in people with the disorder.{{cite journal | vauthors = Hollander E, DeCaria CM, Nitescu A, Gully R, Suckow RF, Cooper TB, Gorman JM, Klein DF, Liebowitz MR | display-authors = 6 | title = Serotonergic function in obsessive-compulsive disorder. Behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers | journal = Archives of General Psychiatry | volume = 49 | issue = 1 | pages = 21–28 | date = January 1992 | pmid = 1728249 | doi = 10.1001/archpsyc.1992.01820010021003 }}{{cite journal | vauthors = Broocks A, Pigott TA, Hill JL, Canter S, Grady TA, L'Heureux F, Murphy DL | title = Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results | journal = Psychiatry Research | volume = 79 | issue = 1 | pages = 11–20 | date = June 1998 | pmid = 9676822 | doi = 10.1016/S0165-1781(98)00029-8 | s2cid = 30339598 | url = https://zenodo.org/record/1259861 }}{{cite journal | vauthors = Pigott TA, Zohar J, Hill JL, Bernstein SE, Grover GN, Zohar-Kadouch RC, Murphy DL | title = Metergoline blocks the behavioral and neuroendocrine effects of orally administered m-chlorophenylpiperazine in patients with obsessive-compulsive disorder | journal = Biological Psychiatry | volume = 29 | issue = 5 | pages = 418–426 | date = March 1991 | pmid = 2018816 | doi = 10.1016/0006-3223(91)90264-M | s2cid = 37648659 }}

mCPP is known to induce headaches in humans and has been used for testing potential antimigraine medications.{{cite journal | vauthors = Leone M, Attanasio A, Croci D, Filippini G, D'Amico D, Grazzi L, Nespolo A, Bussone G | display-authors = 6 | title = The serotonergic agent m-chlorophenylpiperazine induces migraine attacks: A controlled study | journal = Neurology | volume = 55 | issue = 1 | pages = 136–139 | date = July 2000 | pmid = 10891925 | doi = 10.1212/wnl.55.1.136 | s2cid = 27617431 }}{{cite journal | vauthors = Martin RS, Martin GR | title = Investigations into migraine pathogenesis: time course for effects of m-CPP, BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat trigeminal nucleus caudalis (TNC) | journal = Cephalalgia | volume = 21 | issue = 1 | pages = 46–52 | date = February 2001 | pmid = 11298663 | doi = 10.1046/j.1468-2982.2001.00157.x | s2cid = 8471836 | doi-access = free }}{{cite journal | vauthors = Petkov VD, Belcheva S, Konstantinova E | title = Anxiolytic effects of dotarizine, a possible antimigraine drug | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 17 | issue = 10 | pages = 659–668 | date = December 1995 | pmid = 9053586 }} It has potent anorectic effects and has encouraged the development of selective 5-HT_2C receptor agonists for the treatment of obesity as well.{{cite journal | vauthors = Kennett GA, Curzon G | title = Evidence that hypophagia induced by mCPP and TFMPP requires 5-HT1C and 5-HT1B receptors; hypophagia induced by RU 24969 only requires 5-HT1B receptors | journal = Psychopharmacology | volume = 96 | issue = 1 | pages = 93–100 | year = 1988 | pmid = 2906446 | doi = 10.1007/BF02431539 | s2cid = 21417374 }}{{cite journal | vauthors = Sargent PA, Sharpley AL, Williams C, Goodall EM, Cowen PJ | title = 5-HT2C receptor activation decreases appetite and body weight in obese subjects | journal = Psychopharmacology | volume = 133 | issue = 3 | pages = 309–312 | date = October 1997 | pmid = 9361339 | doi = 10.1007/s002130050407 | url = http://link.springer.de/link/service/journals/00213/bibs/7133003/71330309.htm | url-status = dead | s2cid = 7125577 | archive-url = https://web.archive.org/web/20020112063624/http://link.springer.de/link/service/journals/00213/bibs/7133003/71330309.htm | archive-date = 2002-01-12 | url-access = subscription }}{{cite journal | vauthors = Hayashi A, Suzuki M, Sasamata M, Miyata K | title = Agonist diversity in 5-HT(2C) receptor-mediated weight control in rats | journal = Psychopharmacology | volume = 178 | issue = 2–3 | pages = 241–249 | date = March 2005 | pmid = 15719229 | doi = 10.1007/s00213-004-2019-z | s2cid = 7580231 }}{{cite journal | vauthors = Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE | title = Serotonergic drugs : effects on appetite expression and use for the treatment of obesity | journal = Drugs | volume = 67 | issue = 1 | pages = 27–55 | year = 2007 | pmid = 17209663 | doi = 10.2165/00003495-200767010-00004 | s2cid = 46972692 }}

Pharmacology

=Pharmacodynamics=

Site	K_i (nM)	Species	Refs
class="wikitable floatleft" style="font-size:small;" \|+ meta-Chlorophenylpiperazine{{cite web \| title = PDSP K_i Database \| work = Psychoactive Drug Screening Program (PDSP) \| vauthors = Roth BL, Driscol J \|author1-link=Bryan Roth \| publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \| access-date = 14 August 2017 \| url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=1827&testLigand=&refDDRadio=refDDRadio&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}
{{abbrlink\|SERT\|Serotonin transporter}}	202–432	Human	{{cite journal \| vauthors = Owens MJ, Morgan WN, Plott SJ, Nemeroff CB \| title = Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites \| journal = The Journal of Pharmacology and Experimental Therapeutics \| volume = 283 \| issue = 3 \| pages = 1305–1322 \| date = December 1997 \| pmid = 9400006 }}
{{abbrlink\|NET\|Norepinephrine transporter}}	1,940–4,360	Human
{{abbrlink\|DAT\|Dopamine transporter}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}
5-HT_1A	44–400	Human	{{cite journal \| vauthors = Hamik A, Peroutka SJ \| title = 1-(m-chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in the human brain \| journal = Biological Psychiatry \| volume = 25 \| issue = 5 \| pages = 569–575 \| date = March 1989 \| pmid = 2537663 \| doi = 10.1016/0006-3223(89)90217-5 \| s2cid = 46730665 \| doi-access = free }}
5-HT_1B	89–501	Human	{{cite journal \| vauthors = Boess FG, Martin IL \| title = Molecular biology of 5-HT receptors \| journal = Neuropharmacology \| volume = 33 \| issue = 3–4 \| pages = 275–317 \| year = 1994 \| pmid = 7984267 \| doi = 10.1016/0028-3908(94)90059-0 \| s2cid = 35553281 }}
5-HT_1D	210–1,300	Human	{{cite journal \| vauthors = Hamblin MW, Metcalf MA \| title = Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor \| journal = Molecular Pharmacology \| volume = 40 \| issue = 2 \| pages = 143–148 \| date = August 1991 \| pmid = 1652050 }}
5-HT_1E	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}
5-HT_1F	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}
5-HT_2A	32–398	Human	{{cite journal \| vauthors = Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, Chan HW, Eglen RM \| display-authors = 6 \| title = The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors \| journal = British Journal of Pharmacology \| volume = 115 \| issue = 4 \| pages = 622–628 \| date = June 1995 \| pmid = 7582481 \| pmc = 1908489 \| doi = 10.1111/j.1476-5381.1995.tb14977.x }}
5-HT_2B	3.2–63	Human	{{cite journal \| vauthors = Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL \| title = Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications \| journal = Circulation \| volume = 102 \| issue = 23 \| pages = 2836–2841 \| date = December 2000 \| pmid = 11104741 \| doi = 10.1161/01.cir.102.23.2836 \| doi-access = free }}{{cite journal \| vauthors = Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ \| display-authors = 6 \| title = Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells \| journal = British Journal of Pharmacology \| volume = 128 \| issue = 1 \| pages = 13–20 \| date = September 1999 \| pmid = 10498829 \| pmc = 1571597 \| doi = 10.1038/sj.bjp.0702751 }}
5-HT_2C	3.4–251	Human	{{cite journal \| vauthors = Bentley JM, Adams DR, Bebbington D, Benwell KR, Bickerdike MJ, Davidson JE, Dawson CE, Dourish CT, Duncton MA, Gaur S, George AR, Giles PR, Hamlyn RJ, Kennett GA, Knight AR, Malcolm CS, Mansell HL, Misra A, Monck NJ, Pratt RM, Quirk K, Roffey JR, Vickers SP, Cliffe IA \| display-authors = 6 \| title = Indoline derivatives as 5-HT(2C) receptor agonists \| journal = Bioorganic & Medicinal Chemistry Letters \| volume = 14 \| issue = 9 \| pages = 2367–2370 \| date = May 2004 \| pmid = 15081042 \| doi = 10.1016/j.bmcl.2003.05.001 }}
5-HT₃	427	Human
5-HT₄	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}
5-HT_5A	1,354	Human
5-HT₆	1,748	Human
5-HT₇	163	Human
α₁	97–2,900	Human
α_1A	1,386	Human
α_1B	915	Human
α_1D	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}
α₂	112–570	Human
α_2A	145	Human
α_2B	106	Human
α_2C	124	Human
β	2,500	Human
β₁	2,359	Human
β₂	3,474	Human
D₁	7,000	Human
D₂	>10,000	Human
D₃	>10,000	Rat
D₄	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}
D₅	>10,000	Human
H₁	326	Human
mAChRs	>10,000	Human
{{abbrlink\|nAChRs\|Nicotinic acetylcholine receptors}}	>10,000	Human
σ₁	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}
σ₂	8,350	Rat
I₁	759	Rat
{{abbrlink\|VDCC\|Voltage-dependent calcium channel}}	6,043	Rat
class="sortbottom" \| colspan="4" style="width: 1px;" \| Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

mCPP possesses significant affinity for the 5-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₃, and 5-HT₇ receptors, as well as the SERT.{{cite journal | vauthors = Glennon RA | title = Central serotonin receptors as targets for drug research | journal = J Med Chem | volume = 30 | issue = 1 | pages = 1–12 | date = January 1987 | pmid = 3543362 | doi = 10.1021/jm00384a001 | url = | quote = Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites}} It also has some affinity for α₁-adrenergic, α₂-adrenergic, H₁, I₁, and NET.{{cite journal | vauthors = Silverstone PH, Rue JE, Franklin M, Hallis K, Camplin G, Laver D, Cowen PJ | title = The effects of administration of mCPP on psychological, cognitive, cardiovascular, hormonal and MHPG measurements in human volunteers | journal = International Clinical Psychopharmacology | volume = 9 | issue = 3 | pages = 173–178 | date = September 1994 | pmid = 7814826 | doi = 10.1097/00004850-199409000-00005 | s2cid = 25464507 }} It behaves as an agonist at most serotonin receptors.{{cite journal | vauthors = Samanin R, Mennini T, Ferraris A, Bendotti C, Borsini F, Garattini S | title = Chlorophenylpiperazine: a central serotonin agonist causing powerful anorexia in rats | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 308 | issue = 2 | pages = 159–163 | date = August 1979 | pmid = 503247 | doi = 10.1007/BF00499059 | s2cid = 19293115 }}{{cite journal | vauthors = Odagaki Y, Toyoshima R, Yamauchi T | title = Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTPgammaS binding | journal = Journal of Psychopharmacology | volume = 19 | issue = 3 | pages = 235–241 | date = May 2005 | pmid = 15888508 | doi = 10.1177/0269881105051526 | s2cid = 27389008 }} mCPP has been shown to act not only as a serotonin reuptake inhibitor but as a serotonin releasing agent as well.{{cite journal | vauthors = Pettibone DJ, Williams M | title = Serotonin-releasing effects of substituted piperazines in vitro | journal = Biochemical Pharmacology | volume = 33 | issue = 9 | pages = 1531–1535 | date = May 1984 | pmid = 6610423 | doi = 10.1016/0006-2952(84)90424-6 }}

mCPP's strongest actions are at the 5-HT_2B and 5-HT_2C receptors and its discriminative cue is mediated primarily by 5-HT_2C.{{cite journal | vauthors = Callahan PM, Cunningham KA | title = Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP) | journal = European Journal of Pharmacology | volume = 257 | issue = 1–2 | pages = 27–38 | date = May 1994 | pmid = 8082704 | doi = 10.1016/0014-2999(94)90690-4 }}{{cite journal | vauthors = Gommans J, Hijzen TH, Maes RA, Olivier B | title = Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action | journal = Psychopharmacology | volume = 137 | issue = 3 | pages = 292–302 | date = June 1998 | pmid = 9683007 | doi = 10.1007/s002130050622 | url = http://link.springer.de/link/service/journals/00213/bibs/8137003/81370292.htm | url-status = dead | s2cid = 9265150 | archive-url = https://web.archive.org/web/20020112104011/http://link.springer.de/link/service/journals/00213/bibs/8137003/81370292.htm | archive-date = 2002-01-12 | url-access = subscription }} Its negative effects such as anxiety, headaches, and appetite loss are likely mediated by its actions on the 5-HT_2C receptor.{{cite journal | vauthors = Kennett GA, Curzon G | title = Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors | journal = British Journal of Pharmacology | volume = 94 | issue = 1 | pages = 137–147 | date = May 1988 | pmid = 3401632 | pmc = 1853919 | doi = 10.1111/j.1476-5381.1988.tb11508.x }} Other effects of mCPP include nausea, hypoactivity, and penile erection, the latter two the result of increased 5-HT_2C activity and the former likely via 5-HT₃ stimulation.{{cite journal | vauthors = Kłodzińska A, Jaros T, Chojnacka-Wójcik E, Maj J | title = Exploratory hypoactivity induced by m-trifluoromethylphenylpiperazine (TFMPP) and m-chlorophenylpiperazine (m-CPP) | journal = Journal of Neural Transmission. Parkinson's Disease and Dementia Section | volume = 1 | issue = 3 | pages = 207–218 | year = 1989 | pmid = 2775468 | doi = 10.1007/BF02248670 | s2cid = 23471213 }}{{cite journal | vauthors = Walsh AE, Smith KA, Oldman AD, Williams C, Goodall EM, Cowen PJ | title = m-Chlorophenylpiperazine decreases food intake in a test meal | journal = Psychopharmacology | volume = 116 | issue = 1 | pages = 120–122 | date = September 1994 | pmid = 7862925 | doi = 10.1007/BF02244883 | s2cid = 40801166 }}{{cite journal | vauthors = Stancampiano R, Melis MR, Argiolas A | title = Penile erection and yawning induced by 5-HT1C receptor agonists in male rats: relationship with dopaminergic and oxytocinergic transmission | journal = European Journal of Pharmacology | volume = 261 | issue = 1–2 | pages = 149–155 | date = August 1994 | pmid = 8001637 | doi = 10.1016/0014-2999(94)90313-1 }} mCPP is known to induce migraines and this may be mediated by serotonin 5-HT_2B receptor agonism.{{cite journal | vauthors = Segelcke D, Messlinger K | title = Putative role of 5-HT2B receptors in migraine pathophysiology | journal = Cephalalgia | volume = 37 | issue = 4 | pages = 365–371 | date = April 2017 | pmid = 27127104 | doi = 10.1177/0333102416646760 | url = }}

In comparison studies, mCPP has approximately 10-fold selectivity for the human 5-HT_2C receptor over the human 5-HT_2A and 5-HT_2B receptors (K_i = 3.4 nM vs. 32.1 and 28.8 nM).{{cite journal | vauthors = Nelson DL, Lucaites VL, Wainscott DB, Glennon RA | title = Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 359 | issue = 1 | pages = 1–6 | date = January 1999 | pmid = 9933142 | doi = 10.1007/pl00005315 | s2cid = 20150858 }} It acts as a partial agonist of the human 5-HT_2A{{cite journal | vauthors = Grotewiel MS, Chu H, Sanders-Bush E | title = m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine are partial agonists at cloned 5-HT2A receptors expressed in fibroblasts | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 271 | issue = 2 | pages = 1122–1126 | date = November 1994 | pmid = 7965773 | url = https://pubmed.ncbi.nlm.nih.gov/7965773/ | access-date = 2022-10-02 }} and 5-HT_2C{{cite journal | vauthors = Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ | display-authors = 6 | title = Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells | journal = British Journal of Pharmacology | volume = 128 | issue = 1 | pages = 13–20 | date = September 1999 | pmid = 10498829 | pmc = 1571597 | doi = 10.1038/sj.bjp.0702751 }} receptors but as an antagonist of the human 5-HT_2B receptors.{{cite journal | vauthors = Thomas DR, Gager TL, Holland V, Brown AM, Wood MD | title = m-Chlorophenylpiperazine (mCPP) is an antagonist at the cloned human 5-HT2B receptor | journal = NeuroReport | volume = 7 | issue = 9 | pages = 1457–1460 | date = June 1996 | pmid = 8856697 | doi = 10.1097/00001756-199606170-00002 }}

mCPP produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and hence may be hallucinogenic in humans.{{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 = }} Despite this however, mCPP has been described as non-hallucinogenic in humans.{{cite journal | vauthors = Gumpper RH, Roth BL | title = Psychedelics: preclinical insights provide directions for future research | journal = Neuropsychopharmacology | volume = 49 | issue = 1 | pages = 119–127 | date = January 2024 | pmid = 36932180 | doi = 10.1038/s41386-023-01567-7 | url = | pmc = 10700551 }} In any case, hallucinations have occasionally been reported when large doses of mCPP are taken.

=Pharmacokinetics=

mCPP is metabolized via the CYP2D6 isoenzyme by hydroxylation to para-hydroxy-mCPP (p-OH-mCPP) and this plays a major role in its metabolism.{{cite journal | vauthors = Rotzinger S, Fang J, Coutts RT, Baker GB | title = Human CYP2D6 and metabolism of m-chlorophenylpiperazine | journal = Biological Psychiatry | volume = 44 | issue = 11 | pages = 1185–1191 | date = December 1998 | pmid = 9836023 | doi = 10.1016/S0006-3223(97)00483-6 | s2cid = 45097940 }} The elimination half-life of mCPP is 4 to 14 hours.

mCPP is a metabolite of a variety of other piperazine drugs including trazodone, nefazodone, etoperidone, mepiprazole, cloperidone, peraclopone, and BRL-15,572.{{cite journal | vauthors = Elliott S | title = Current awareness of piperazines: pharmacology and toxicology | journal = Drug Testing and Analysis | volume = 3 | issue = 7–8 | pages = 430–438 | year = 2011 | pmid = 21744514 | doi = 10.1002/dta.307 }}{{Additional citation needed|date=September 2017}} It is formed by dealkylation via CYP3A4. Caution should be exercised in concomitant administration of CYP2D6 inhibitors such as bupropion, fluoxetine, paroxetine, and thioridazine with drugs that produce mCPP as a metabolite as these drugs are known to increase concentrations of the parent molecule (e.g., trazodone) and of mCPP.

Chemistry

=Analogues=

Analogues of mCPP include:

1-Benzylpiperazine (BZP)
1-Methyl-4-benzylpiperazine (MBZP)
1,4-Dibenzylpiperazine (DBZP)
3-Trifluoromethylphenylpiperazine (TFMPP)
3,4-Methylenedioxy-1-benzylpiperazine (MDBZP)
4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP)
4-Fluorophenylpiperazine (pFPP)
4-Methoxyphenylpiperazine (MeOPP)

Some additional analogues include quipazine, ORG-12962, and 3C-PEP.

Society and culture

Image:MCPP tablets.jpg in Vernon Hills, Illinois.]]

Image:M-CPP Tablet 2008 -Kripo 2009 10 09.jpg in Europe at the end of 2008.]]

=Legal status=

==Belgium==

mCPP is illegal in Belgium.{{Cite web|url=http://www.emcdda.europa.eu//html.cfm//index5176EN.html?sLanguageISO=EN&nNodeID=5176&pluginMethod=eldd.shownewsdetails&id=20/12/2006BELGIUM:+New+substances+controlled+include+mCPP+and+khat|title=EMCDDA | News|website=www.emcdda.europa.eu}}

==Brazil==

mCPP is illegal in Brazil.{{Cite web|url=http://www.anvisa.gov.br/divulga/noticias/2008/051108_2.htm|title=ANVISA resolution - Portaria SVS/MS 344/98}}

==Canada==

mCPP is not a controlled drug in Canada.

==China==

As of October 2015 mCPP 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 | archive-date=1 October 2015 | archive-url=https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html | url-status=dead }}

==Czech Republic==

mCPP is legal in the Czech Republic.{{Cite web|url=http://www.mzcr.cz/Odbornik/obsah/legislativa_1051_3.html|title=Legislativa|website=www.mzcr.cz}}

==Denmark==

mCPP is illegal in Denmark.{{Cite web|url=https://www.erowid.org/psychoactives/law/countries/denmark/denmark_law_info1.shtml|title=Erowid Psychoactive Vaults : Law : Countries : Denmark (DK) : Denmark bans 2C-T-4, TFMPP, BZP, mCPP, MeOPP|website=www.erowid.org}}{{unreliable source?|date=May 2016}}

==Finland==

mCPP is illegal in Finland.

==Germany==

mCPP is illegal in Germany.

==Hungary==

mCPP is illegal in Hungary since 2012.

==Japan==

mCPP is illegal in Japan since 2006.

==Netherlands==

mCPP is legal in the Netherlands.{{Cite web|url=https://wetten.overheid.nl/BWBR0001941/2017-05-25|title=Opiumwet|first=Ministerie van Binnenlandse Zaken en|last=Koninkrijksrelaties|website=wetten.overheid.nl}}

==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.{{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}} However, mCPP is legally used for scientific research.

==Norway==

mCPP is illegal in Norway.

==Russia==

mCPP is illegal in Russia.

==Sweden==

mCPP is illegal in Sweden.

==Poland==

mCPP is illegal in Poland.

==United States==

mCPP is not scheduled at the federal level in the United States,{{Cite web |url=http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm |title=21 CFR — SCHEDULES OF CONTROLLED SUBSTANCES §1308.11 Schedule I. |access-date=2014-12-18 |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 is possible that it could be considered a controlled substance analog of BZP, in which case purchase, sale, or possession could be prosecuted under the Federal Analog Act.

However, "chlorophenylpiperazine" is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in this state.{{Cite web|url=http://leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0800-0899/0893/0893.html|title=Statutes & Constitution :View Statutes : Online Sunshine|website=leg.state.fl.us}}

United Arab Emirates

mCPP is illegal in the UAE, the country has strict drug laws, and many psychoactive substances are classified as controlled or prohibited.{{Cite web |title=Drugs {{!}} The Official Portal of the UAE Government |url=https://u.ae/en/information-and-services/health-and-fitness/drugs-and-controlled-medicines/drugs |archive-url=http://web.archive.org/web/20250328034257/https://u.ae/en/information-and-services/health-and-fitness/drugs-and-controlled-medicines/drugs |archive-date=2025-03-28 |access-date=2025-06-09 |website=u.ae |language=en}}

==Turkey==

mCPP is illegal in Turkey since 20/05/2009.{{Cite web|url=https://www.resmigazete.gov.tr/eskiler/2009/05/20090520-3.htm|title = Başbakanlık Mevzuatı Geliştirme ve Yayın Genel Müdürlüğü}}