Meta-Chlorophenylpiperazine Explained

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.[1] [2] 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.[3] [4]

Despite its advertisement as a recreational substance, mCPP is actually generally considered to be an unpleasant experience and is not desired by drug users.[3] It lacks any reinforcing effects, but has "psychostimulant, anxiety-provoking, and hallucinogenic effects."[5] [6] [7] It is also known to produce dysphoric, depressive, and anxiogenic effects in rodents and humans,[8] [9] and can induce panic attacks in individuals susceptible to them.[10] [11] [12] [13] It also worsens obsessive–compulsive symptoms in people with the disorder.[14] [15] [16]

mCPP is known to induce headaches in humans and has been used for testing potential antimigraine medications.[17] [18] [19] It has potent anorectic effects and has encouraged the development of selective 5-HT2C receptor agonists for the treatment of obesity as well.[20] [21] [22] [23]

Pharmacology

Pharmacodynamics

meta-Chlorophenylpiperazine[24]
Site Ki (nM) Species Refs
202–432 Human [25]
1,940–4,360 Human
44–400 Human [26]
89–501 Human [27]
210–1,300 Human [28]
32–398 Human [29]
3.2–63 Human [30] [31]
3.4–251 Human [32]
427 Human
5-HT5A  1,354 Human
1,748 Human
163 Human
97–2,900 Human
1,386 Human
915 Human
112–570 Human
145 Human
106 Human
124 Human
2,500 Human
2,359 Human
3,474 Human
7,000 Human
>10,000 Human
>10,000 Rat
>10,000 Human
326 Human
>10,000 Human
>10,000 Human
8,350 Rat
759 Rat
6,043 Rat
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

mCPP possesses significant affinity for the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, and 5-HT7 receptors, as well as the SERT. It also has some affinity for α1-adrenergic, α2-adrenergic, H1, I1, and NET.[33] It behaves as an agonist at most serotonin receptors.[34] [35] mCPP has been shown to act not only as a serotonin reuptake inhibitor but as a serotonin releasing agent as well.[36]

mCPP's strongest actions are at the 5-HT2B and 5-HT2C receptors and its discriminative cue is mediated primarily by 5-HT2C.[24] [37] [38] Its negative effects such as anxiety, headaches, and appetite loss are likely mediated by its actions on the 5-HT2C receptor.[9] [20] [39] Other effects of mCPP include nausea, hypoactivity, and penile erection, the latter two the result of increased 5-HT2C activity and the former likely via 5-HT3 stimulation.[40] [41] [42]

In comparison studies, mCPP has approximately 10-fold selectivity for the human 5-HT2C receptor over the human 5-HT2A and 5-HT2B receptors (Ki = 3.4 nM vs. 32.1 and 28.8 nM).[43] It acts as a partial agonist of the human 5-HT2A[44] and 5-HT2C[45] receptors but as an antagonist of the human 5-HT2B receptors.[46]

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.[47] 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, enpiprazole, mepiprazole, cloperidone, peraclopone, and BRL-15,572.[48] 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:

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

Society and culture

Legal status

Belgium

mCPP is illegal in Belgium.[49]

Brazil

mCPP is illegal in Brazil.[50]

Canada

mCPP is not a controlled drug in Canada.

China

As of October 2015 mCPP is a controlled substance in China.[51]

Czech Republic

mCPP is legal in the Czech Republic.[52]

Denmark

mCPP is illegal in Denmark.[53]

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.[54]

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.[55] 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,[56] 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.[57]

Turkey

mCPP is illegal in Turkey since 20/05/2009.[58]

See also

Notes and References

  1. Bossong MG, Van Dijk JP, Niesink RJ . Methylone and mCPP, two new drugs of abuse? . Addiction Biology . 10 . 4 . 321–323 . December 2005 . 16318952 . 10.1080/13556210500350794 . dead . 36169592 . 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 . 2013-01-05 .
  2. Lecompte Y, Evrard I, Arditti J . [Metachlorophenylpiperazine (mCPP): a new designer drug] . fr . Therapie . 61 . 6 . 523–530 . 2006 . 17348609 . 10.2515/therapie:2006093 .
  3. Bossong MG, Brunt TM, Van Dijk JP, Rigter SM, Hoek J, Goldschmidt HM, Niesink RJ . mCPP: an undesired addition to the ecstasy market . Journal of Psychopharmacology . 24 . 9 . 1395–1401 . September 2010 . 19304863 . 10.1177/0269881109102541 . 11186375 .
  4. Vogels N, Brunt TM, Rigter S, van Dijk P, Vervaeke H, Niesink RJ . Content of ecstasy in the Netherlands: 1993-2008 . Addiction . 104 . 12 . 2057–2066 . December 2009 . 19804461 . 10.1111/j.1360-0443.2009.02707.x . free .
  5. Web site: World Health Organization. 1-(3-chlorophenyl) piperazine (mCPP) - Expert peer review on pre-review report. 2021-01-12.
  6. Tancer ME, Johanson CE . The subjective effects of MDMA and mCPP in moderate MDMA users . Drug and Alcohol Dependence . 65 . 1 . 97–101 . December 2001 . 11714594 . 10.1016/s0376-8716(01)00146-6 .
  7. Tancer M, Johanson CE . Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP . Drug and Alcohol Dependence . 72 . 1 . 33–44 . October 2003 . 14563541 . 10.1016/S0376-8716(03)00172-8 .
  8. Rajkumar R, Pandey DK, Mahesh R, Radha R . 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 . European Journal of Pharmacology . 608 . 1–3 . 32–41 . April 2009 . 19269287 . 10.1016/j.ejphar.2009.02.041 .
  9. Kennett GA, Whitton P, Shah K, Curzon G . Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists . European Journal of Pharmacology . 164 . 3 . 445–454 . May 1989 . 2767117 . 10.1016/0014-2999(89)90252-5 .
  10. Klein E, Zohar J, Geraci MF, Murphy DL, Uhde TW . Anxiogenic effects of m-CPP in patients with panic disorder: comparison to caffeine's anxiogenic effects . Biological Psychiatry . 30 . 10 . 973–984 . November 1991 . 1756202 . 10.1016/0006-3223(91)90119-7 . 43010184 .
  11. Charney DS, Woods SW, Goodman WK, Heninger GR . Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects . Psychopharmacology . 92 . 1 . 14–24 . 1987 . 3110824 . 10.1007/bf00215473 . 43079787 .
  12. Van Veen JF, Van der Wee NJ, Fiselier J, Van Vliet IM, Westenberg HG . Behavioural effects of rapid intravenous administration of meta-chlorophenylpiperazine (m-CPP) in patients with generalized social anxiety disorder, panic disorder and healthy controls . European Neuropsychopharmacology . 17 . 10 . 637–642 . October 2007 . 17481859 . 10.1016/j.euroneuro.2007.03.005 . 41601926 .
  13. van der Wee NJ, Fiselier J, van Megen HJ, Westenberg HG . Behavioural effects of rapid intravenous administration of meta-chlorophenylpiperazine in patients with panic disorder and controls . European Neuropsychopharmacology . 14 . 5 . 413–417 . October 2004 . 15336303 . 10.1016/j.euroneuro.2004.01.001 . 28987431 .
  14. Hollander E, DeCaria CM, Nitescu A, Gully R, Suckow RF, Cooper TB, Gorman JM, Klein DF, Liebowitz MR . 6 . Serotonergic function in obsessive-compulsive disorder. Behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers . Archives of General Psychiatry . 49 . 1 . 21–28 . January 1992 . 1728249 . 10.1001/archpsyc.1992.01820010021003 .
  15. Broocks A, Pigott TA, Hill JL, Canter S, Grady TA, L'Heureux F, Murphy DL . Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results . Psychiatry Research . 79 . 1 . 11–20 . June 1998 . 9676822 . 10.1016/S0165-1781(98)00029-8 . 30339598 .
  16. Pigott TA, Zohar J, Hill JL, Bernstein SE, Grover GN, Zohar-Kadouch RC, Murphy DL . Metergoline blocks the behavioral and neuroendocrine effects of orally administered m-chlorophenylpiperazine in patients with obsessive-compulsive disorder . Biological Psychiatry . 29 . 5 . 418–426 . March 1991 . 2018816 . 10.1016/0006-3223(91)90264-M . 37648659 .
  17. Leone M, Attanasio A, Croci D, Filippini G, D'Amico D, Grazzi L, Nespolo A, Bussone G . 6 . The serotonergic agent m-chlorophenylpiperazine induces migraine attacks: A controlled study . Neurology . 55 . 1 . 136–139 . July 2000 . 10891925 . 10.1212/wnl.55.1.136 . 27617431 .
  18. Martin RS, Martin GR . 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) . Cephalalgia . 21 . 1 . 46–52 . February 2001 . 11298663 . 10.1046/j.1468-2982.2001.00157.x . 8471836 . free .
  19. Petkov VD, Belcheva S, Konstantinova E . Anxiolytic effects of dotarizine, a possible antimigraine drug . Methods and Findings in Experimental and Clinical Pharmacology . 17 . 10 . 659–668 . December 1995 . 9053586 .
  20. Kennett GA, Curzon G . 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 . Psychopharmacology . 96 . 1 . 93–100 . 1988 . 2906446 . 10.1007/BF02431539 . 21417374 .
  21. Sargent PA, Sharpley AL, Williams C, Goodall EM, Cowen PJ . 5-HT2C receptor activation decreases appetite and body weight in obese subjects . Psychopharmacology . 133 . 3 . 309–312 . October 1997 . 9361339 . 10.1007/s002130050407 . dead . 7125577 . https://web.archive.org/web/20020112063624/http://link.springer.de/link/service/journals/00213/bibs/7133003/71330309.htm . 2002-01-12 .
  22. Hayashi A, Suzuki M, Sasamata M, Miyata K . Agonist diversity in 5-HT(2C) receptor-mediated weight control in rats . Psychopharmacology . 178 . 2–3 . 241–249 . March 2005 . 15719229 . 10.1007/s00213-004-2019-z . 7580231 .
  23. Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE . Serotonergic drugs : effects on appetite expression and use for the treatment of obesity . Drugs . 67 . 1 . 27–55 . 2007 . 17209663 . 10.2165/00003495-200767010-00004 . 46972692 .
  24. Web site: PDSP Ki Database . Psychoactive Drug Screening Program (PDSP) . Roth BL, Driscol J . Bryan Roth . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . 14 August 2017 .
  25. Owens MJ, Morgan WN, Plott SJ, Nemeroff CB . Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites . The Journal of Pharmacology and Experimental Therapeutics . 283 . 3 . 1305–1322 . December 1997 . 9400006 .
  26. Hamik A, Peroutka SJ . 1-(m-chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in the human brain . Biological Psychiatry . 25 . 5 . 569–575 . March 1989 . 2537663 . 10.1016/0006-3223(89)90217-5 . 46730665 .
  27. Boess FG, Martin IL . Molecular biology of 5-HT receptors . Neuropharmacology . 33 . 3–4 . 275–317 . 1994 . 7984267 . 10.1016/0028-3908(94)90059-0 . 35553281 .
  28. Hamblin MW, Metcalf MA . Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor . Molecular Pharmacology . 40 . 2 . 143–148 . August 1991 . 1652050 .
  29. Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, Chan HW, Eglen RM . 6 . The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors . British Journal of Pharmacology . 115 . 4 . 622–628 . June 1995 . 7582481 . 1908489 . 10.1111/j.1476-5381.1995.tb14977.x .
  30. Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL . Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications . Circulation . 102 . 23 . 2836–2841 . December 2000 . 11104741 . 10.1161/01.cir.102.23.2836 . free .
  31. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ . 6 . Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells . British Journal of Pharmacology . 128 . 1 . 13–20 . September 1999 . 10498829 . 1571597 . 10.1038/sj.bjp.0702751 .
  32. 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 . 6 . Indoline derivatives as 5-HT(2C) receptor agonists . Bioorganic & Medicinal Chemistry Letters . 14 . 9 . 2367–2370 . May 2004 . 15081042 . 10.1016/j.bmcl.2003.05.001 .
  33. Silverstone PH, Rue JE, Franklin M, Hallis K, Camplin G, Laver D, Cowen PJ . The effects of administration of mCPP on psychological, cognitive, cardiovascular, hormonal and MHPG measurements in human volunteers . International Clinical Psychopharmacology . 9 . 3 . 173–178 . September 1994 . 7814826 . 10.1097/00004850-199409000-00005 . 25464507 .
  34. Samanin R, Mennini T, Ferraris A, Bendotti C, Borsini F, Garattini S . Chlorophenylpiperazine: a central serotonin agonist causing powerful anorexia in rats . Naunyn-Schmiedeberg's Archives of Pharmacology . 308 . 2 . 159–163 . August 1979 . 503247 . 10.1007/BF00499059 . 19293115 .
  35. Odagaki Y, Toyoshima R, Yamauchi T . Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTPgammaS binding . Journal of Psychopharmacology . 19 . 3 . 235–241 . May 2005 . 15888508 . 10.1177/0269881105051526 . 27389008 .
  36. Pettibone DJ, Williams M . Serotonin-releasing effects of substituted piperazines in vitro . Biochemical Pharmacology . 33 . 9 . 1531–1535 . May 1984 . 6610423 . 10.1016/0006-2952(84)90424-6 .
  37. Callahan PM, Cunningham KA . Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP) . European Journal of Pharmacology . 257 . 1–2 . 27–38 . May 1994 . 8082704 . 10.1016/0014-2999(94)90690-4 .
  38. Gommans J, Hijzen TH, Maes RA, Olivier B . Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action . Psychopharmacology . 137 . 3 . 292–302 . June 1998 . 9683007 . 10.1007/s002130050622 . dead . 9265150 . https://web.archive.org/web/20020112104011/http://link.springer.de/link/service/journals/00213/bibs/8137003/81370292.htm . 2002-01-12 .
  39. Kennett GA, Curzon G . Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors . British Journal of Pharmacology . 94 . 1 . 137–147 . May 1988 . 3401632 . 1853919 . 10.1111/j.1476-5381.1988.tb11508.x .
  40. Kłodzińska A, Jaros T, Chojnacka-Wójcik E, Maj J . Exploratory hypoactivity induced by m-trifluoromethylphenylpiperazine (TFMPP) and m-chlorophenylpiperazine (m-CPP) . Journal of Neural Transmission. Parkinson's Disease and Dementia Section . 1 . 3 . 207–218 . 1989 . 2775468 . 10.1007/BF02248670 . 23471213 .
  41. Walsh AE, Smith KA, Oldman AD, Williams C, Goodall EM, Cowen PJ . m-Chlorophenylpiperazine decreases food intake in a test meal . Psychopharmacology . 116 . 1 . 120–122 . September 1994 . 7862925 . 10.1007/BF02244883 . 40801166 .
  42. Stancampiano R, Melis MR, Argiolas A . Penile erection and yawning induced by 5-HT1C receptor agonists in male rats: relationship with dopaminergic and oxytocinergic transmission . European Journal of Pharmacology . 261 . 1–2 . 149–155 . August 1994 . 8001637 . 10.1016/0014-2999(94)90313-1 .
  43. Nelson DL, Lucaites VL, Wainscott DB, Glennon RA . Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors . Naunyn-Schmiedeberg's Archives of Pharmacology . 359 . 1 . 1–6 . January 1999 . 9933142 . 10.1007/pl00005315 . 20150858 .
  44. Grotewiel MS, Chu H, Sanders-Bush E . m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine are partial agonists at cloned 5-HT2A receptors expressed in fibroblasts . The Journal of Pharmacology and Experimental Therapeutics . 271 . 2 . 1122–1126 . November 1994 . 7965773 . 2022-10-02 .
  45. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ . 6 . Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells . British Journal of Pharmacology . 128 . 1 . 13–20 . September 1999 . 10498829 . 1571597 . 10.1038/sj.bjp.0702751 .
  46. Thomas DR, Gager TL, Holland V, Brown AM, Wood MD . m-Chlorophenylpiperazine (mCPP) is an antagonist at the cloned human 5-HT2B receptor . NeuroReport . 7 . 9 . 1457–1460 . June 1996 . 8856697 . 10.1097/00001756-199606170-00002 .
  47. Rotzinger S, Fang J, Coutts RT, Baker GB . Human CYP2D6 and metabolism of m-chlorophenylpiperazine . Biological Psychiatry . 44 . 11 . 1185–1191 . December 1998 . 9836023 . 10.1016/S0006-3223(97)00483-6 . 45097940 .
  48. Elliott S . Current awareness of piperazines: pharmacology and toxicology . Drug Testing and Analysis . 3 . 7–8 . 430–438 . 2011 . 21744514 . 10.1002/dta.307 .
  49. Web site: EMCDDA | News. www.emcdda.europa.eu.
  50. Web site: ANVISA resolution - Portaria SVS/MS 344/98.
  51. Web site: 关于印发《非药用类麻醉药品和精神药品列管办法》的通知 . China Food and Drug Administration . 27 September 2015 . zh . 1 October 2015 . 1 October 2015 . https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html . dead .
  52. Web site: Legislativa. www.mzcr.cz.
  53. Web site: Erowid Psychoactive Vaults : Law : Countries : Denmark (DK) : Denmark bans 2C-T-4, TFMPP, BZP, mCPP, MeOPP. www.erowid.org.
  54. Web site: Opiumwet. Ministerie van Binnenlandse Zaken en. Koninkrijksrelaties. wetten.overheid.nl.
  55. Web site: Misuse of Drugs (Classification of BZP) Amendment Bill 2008.
  56. Web site: 21 CFR — SCHEDULES OF CONTROLLED SUBSTANCES §1308.11 Schedule I. . 2014-12-18 . 2009-08-27 . https://web.archive.org/web/20090827043725/http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm . dead .
  57. Web site: Statutes & Constitution :View Statutes : Online Sunshine. leg.state.fl.us.
  58. Web site: Başbakanlık Mevzuatı Geliştirme ve Yayın Genel Müdürlüğü.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Meta-Chlorophenylpiperazine".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.