meta-Chlorophenylpiperazine (mCPP) belongs to the phenylpiperazine class of psychoactive drugs. Originally developed for scientific research purposes in the late 1970s, it later found its way into the designer drug market in the mid-2000s. Notably, mCPP has been identified in pills marketed as legal alternatives to illicit stimulants in New Zealand, and it has also been detected in pills sold as “ecstasy” in Europe and the United States.
Despite being marketed as a recreational substance, mCPP is widely recognized as an unpleasant experience and generally undesirable among drug users. It lacks reinforcing effects but is associated with psychostimulant, anxiety-inducing, and hallucinogenic effects. Additionally, it is known to induce dysphoria, depression, and anxiety in both rodents and humans. For individuals susceptible to panic attacks, mCPP has been reported to trigger such episodes. Moreover, it exacerbates symptoms in individuals with obsessive-compulsive disorder.
Notably, mCPP has a reputation for causing headaches in humans and has been employed in the testing of potential antimigraine medications. Furthermore, due to its potent anorectic (appetite-suppressing) effects, it has spurred the development of selective 5-HT2C receptor agonists as potential treatments for obesity.
|CompTox Dashboard (EPA)||DTXSID9045138|
|Chemical and physical data|
|Molar mass||196.68 g·mol−1|
mCPP exhibits notable affinity for various serotonin receptors, including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, and 5-HT7 receptors, in addition to the serotonin transporter (SERT). It also displays some affinity for α1-adrenergic, α2-adrenergic, H1, I1, and NET receptors. mCPP predominantly acts as an agonist at most serotonin receptors. Remarkably, it functions both as a serotonin reuptake inhibitor and a serotonin-releasing agent.
The most pronounced effects of mCPP are observed at the 5-HT2B and 5-HT2C receptors. Its discriminative cue is primarily mediated through the 5-HT2C receptor. Undesirable effects associated with mCPP, such as anxiety, headaches, and reduced appetite, are likely attributed to its actions on the 5-HT2C receptor. Additionally, mCPP can induce nausea, decreased activity, and penile erections, with the latter two effects resulting from increased 5-HT2C activity and the former likely due to 5-HT3 receptor stimulation.
In comparative studies, mCPP displays approximately 10-fold selectivity for the human 5-HT2C receptor over the human 5-HT2A and 5-HT2B receptors (with Ki values of 3.4 nM, 32.1 nM, and 28.8 nM, respectively). It acts as a partial agonist of human 5-HT2A and 5-HT2C receptors but functions as an antagonist of the human 5-HT2B receptors.
mCPP undergoes metabolism primarily through the CYP2D6 isoenzyme, involving hydroxylation to form para-hydroxy-mCPP (p-OH-mCPP), which plays a significant role in its metabolism. The elimination half-life of mCPP falls within the range of 4 to 14 hours.
mCPP is a metabolite of various other piperazine-based drugs, including trazodone, nefazodone, etoperidone, enpiprazole, mepiprazole, cloperidone, peraclopone, and BRL-15,572. This metabolite is formed via dealkylation facilitated by the CYP3A4 enzyme. It is essential to exercise caution when administering drugs that produce mCPP as a metabolite concurrently with CYP2D6 inhibitors like bupropion, fluoxetine, paroxetine, and thioridazine, as these combinations are known to elevate concentrations of both the parent compound (e.g., trazodone) and mCPP.
Society and culture
- Belgium: mCPP is illegal in Belgium.
- Brazil: mCPP is illegal in Brazil.
- Canada: mCPP is not a controlled drug in Canada.
- China: As of October 2015, mCPP is a controlled substance in China.
- Czech Republic: mCPP is legal in the Czech Republic.
- Denmark: mCPP is illegal in Denmark.
- Finland: mCPP is illegal in Finland.
- Germany: mCPP is illegal in Germany.
- Hungary: mCPP has been illegal in Hungary since 2012.
- Japan: mCPP has been illegal in Japan since 2006.
- Netherlands: mCPP is legal in the Netherlands.
- New Zealand: Following the recommendation of the EACD, the New Zealand government passed legislation that placed BZP, as well as other piperazine derivatives (TFMPP, mCPP, pFPP, MeOPP, and MBZP), into Class C of the New Zealand Misuse of Drugs Act 1975. Although the ban was initially intended to take effect on December 18, 2007, the law change was enacted the following year. Consequently, the sale of BZP and the other listed piperazines became illegal in New Zealand as of April 1, 2008. An amnesty for possession and usage of these drugs remained in place until October 2008, after which they became entirely illegal. However, it is essential to note that mCPP is legally available 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 classified at the federal level in the United States. However, it could be considered a controlled substance analogue of BZP, and as such, its purchase, sale, or possession may be subject to prosecution under the Federal Analog Act. Notably, “chlorophenylpiperazine” is classified as a Schedule I controlled substance in the state of Florida, making it illegal to buy, sell, or possess within the state.
- Turkey: mCPP has been illegal in Turkey since May 20, 2009.
1. What is mCPP (meta-chlorophenylpiperazine)?
mCPP is a psychoactive drug belonging to the phenylpiperazine class. It was initially developed for scientific research but later found its way into recreational use.
2. What effects does mCPP produce?
mCPP is known for its psychostimulant, anxiety-provoking, and hallucinogenic effects. It also induces headaches and nausea. Although it has been marketed as a recreational substance, it is generally considered an unpleasant experience by users.
3. What is mCPP’s mechanism of action?
mCPP primarily affects various serotonin receptors, including 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, and 5-HT7 receptors, as well as the serotonin transporter (SERT). It acts as an agonist at most serotonin receptors.
4. How is mCPP metabolized?
mCPP is metabolized through the CYP2D6 isoenzyme, primarily by hydroxylation to para-hydroxy-mCPP (p-OH-mCPP). This metabolite plays a significant role in its metabolism. The elimination half-life of mCPP is 4 to 14 hours.
5. Is mCPP legal in my country?
The legal status of mCPP varies by country. It is essential to check your local laws. In some countries, such as Belgium, Brazil, Denmark, Finland, Germany, Hungary, Japan, Norway, Russia, Sweden, and Poland, mCPP is illegal. In contrast, it is legal in the Netherlands for scientific research purposes.
6. Is mCPP legal in the United States?
At the federal level in the United States, mCPP is not scheduled. However, it could be considered a controlled substance analogue of BZP, which might result in prosecution under the Federal Analog Act. Furthermore, in the state of Florida, “chlorophenylpiperazine” is a Schedule I controlled substance, making it illegal.
7. Is mCPP available for scientific research?
Yes, in some places like the Netherlands and New Zealand, mCPP is legally used for scientific research.
8. What are the side effects of mCPP?
Common side effects of mCPP use include anxiety, headaches, appetite loss, nausea, and hallucinogenic effects. It has also been known to induce panic attacks in susceptible individuals and worsen obsessive–compulsive symptoms.
9. What is the history of mCPP?
mCPP was developed for scientific research in the late 1970s but later became available as a designer drug for recreational use in the mid-2000s. It has been marketed as a legal alternative to illicit stimulants.
10. Does mCPP have any medical applications?
mCPP has been used in testing potential antimigraine medications due to its ability to induce headaches in humans. Additionally, its potent anorectic effects have led to research into selective 5-HT2C receptor agonists for the treatment of obesity.
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