M-chlorophenylpiperazine

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. 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. 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. 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. 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 or hallucinogenic effects, produces dysphoric, depressive, and anxiogenic effects in rodents and humans, and can induce panic attacks in individuals susceptible to them. It also worsens obsessive–compulsive symptoms in people with the disorder. mCPP is known to induce headaches in humans and has been used for testing potential antimigraine medications. It has potent anorectic effects and has encouraged the development of selective 5-HT2C receptor agonists for the treatment of obesity as well. 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. It behaves as an agonist at most serotonin receptors. mCPP has been shown to act not only as a serotonin reuptake inhibitor but as a serotonin releasing agent as well. mCPP's strongest actions are at the 5-HT2B and 5-HT2C receptors and its discriminative cue is mediated primarily by 5-HT2C. Its negative effects such as anxiety, headaches, and appetite loss are likely mediated by its actions on the 5-HT2C receptor. 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. 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). It acts as a partial agonist of the human 5-HT2C receptor but as an antagonist of the human 5-HT2A and 5-HT2B receptors. In accordance with its lack of agonism towards the human 5-HT2A receptor, there are no reports that mCPP produces hallucinogenic effects in humans. mCPP is metabolized via the CYP2D6 isoenzyme by hydroxylation to para-hydroxy-mCPP (p-OH-mCPP). Caution should be exercised in coprescribing inhibitors or substrates of CYP2D6 with drugs such as trazodone and nefazodone that have mCPP as a metabolite. mCPP is a metabolite of a variety of other piperazine drugs including trazodone, nefazodone, etoperidone, enpiprazole, mepiprazole, cloperidone, peraclopone, and BRL-15,572. It is formed by dealkylation via CYP3A4. Analogues of mCPP include: