1-(3-Chlorophenyl)piperazine - AbsoluteAstronomy.com

meta-Chlorophenylpiperazine (mCPP) is a psychoactive drug

Psychoactive drug

A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...

of the phenylpiperazine

Phenylpiperazine

1-Phenylpiperazine is a simple chemical compound featuring a phenyl group bound to a piperazine ring. The suffix '-piprazole' is sometimes used in the names of drugs to indicate they belong to this class....

class. It was initially developed in the late-1970s and used in scientific research before being sold as a designer drug

Designer drug

Designer drug is a term used to describe drugs that are created to get around existing drug laws, usually by preparing analogs or derivatives of existing drugs by modifying their chemical structure to varying degrees, or less commonly by finding drugs with entirely different chemical structures...

in the mid-2000s. It has been detected in pills touted as legal alternatives to illicit stimulant

Stimulant

Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

s in New Zealand

New Zealand

New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...

and pills sold as "ecstasy" in Europe

Europe

Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

and the United States

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

.

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, produces depressive

Depression (mood)

Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

and anxiogenic

Anxiogenic

An anxiogenic substance is one that causes anxiety. Anxiogenic effects can be measured by, for example, the hole-board test in rats and mice. A number of agents are used to provoke anxiety or panic in experimental models...

effects in rodents and humans, and can induce panic attack

Panic attack

Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...

s in individuals susceptible to them. It also worsens obsessive-compulsive

Obsessive-compulsive disorder

Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...

symptoms in people with the disorder.

mCPP is known to induce headache

Headache

A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

s in humans and has been used for testing potential antimigraine

Antimigraine

An antimigraine drug is a medication intended to reduce the effects or intensity of migraine headache.Examples are the triptans, including zolmitriptan....

medications. It has potent anorectic

Anorectic

An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...

effects and has encouraged the development of selective 5-HT_2C receptor

5-HT2C receptor

The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the...

agonist

Agonist

An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

s for the treatment of obesity

Obesity

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

as well.

Meta-chlorophenylpiperazine is a major metabolite of the psychotropic drug trazodone

Trazodone

Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...

, and may be responsible for some of its side-effects, such as headaches and migraines induced many hours after initial consumption.

Pharmacology

mCPP possesses significant affinity for the 5-HT_1A

5-HT1A receptor

The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...

, 5-HT_1B

5-HT1B receptor

5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT1B receptor is a 5-HT receptor subtype.-Tissue distribution and function:...

, 5-HT_1D

5-HT1D receptor

5-hydroxytryptamine receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it. 5-HT1D acts on the central nervous system, and affects locomotion and anxiety...

, 5-HT_2A

5-HT2A receptor

The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...

, 5-HT_2B

5-HT2B receptor

5-hydroxytryptamine receptor 2B, also known as HTR2B, is a 5-HT2 receptor, but also denotes the human gene encoding it.-Function:...

, 5-HT_2C

5-HT2C receptor

, 5-HT₃

5-HT3 receptor

The 5-HT3 receptor is a member of the superfamily of ligand-gated ion channels, a superfamily that also includes the neuronal nicotinic acetylcholine receptors , and the inhibitory neurotransmitter receptors for GABA and glycine...

, and 5-HT₇ receptor

5-HT7 receptor

The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin The 5-HT7 receptor is coupled to Gs and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various...

s, as well as the SERT

Serotonin transporter

The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

. It also has some affinity for α₁-adrenergic, α₂-adrenergic, H₁

H1 receptor

The H1 receptor is a histamine receptor belonging to the family of Rhodopsin like G-protein-coupled receptors. This receptor, which is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, in smooth muscles, on vascular endothelial cells, in the heart, and in...

, I₁

Imidazoline receptor

Imidazoline receptors are receptors for clonidine and other imidazolines.-Classes:There are three classes of imidazoline receptors:* I1 receptor – mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure, * I2 receptor – an allosteric binding site of monoamine oxidase and is...

, and NET

Norepinephrine transporter

The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....

. It behaves as an agonist

Agonist

An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

at most or all serotonin receptors. mCPP has been shown to act not only as a reuptake inhibitor

Reuptake inhibitor

A reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...

of serotonin but as a releasing agent

Releasing agent

A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...

as well.

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. Its negative effects such as anxiety

Anxiety

Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, headache

Headache

s, and appetite loss

Anorexia (symptom)

Anorexia is the decreased sensation of appetite...

are likely mediated by its actions on the 5-HT_2C receptor, whereas its psychedelic

Psychedelic drug

A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...

effects at high doses are caused by 5-HT_2A activation. Other effects of mCPP include nausea

Nausea

Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, hypoactivity

Hypoactivity

Hypoactivity is inhibition of behavioral or locomotor activity.Some drugs such as antipsychotics and mCPP produce this effect....

, and penile erection, the latter two the result of increased 5-HT_2C activity and the former likely via 5-HT₃ stimulation.

Pharmacokinetics

mCPP is metabolized via the CYP2D6

CYP2D6

Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

isoenzyme by hydroxylation

Hydroxylation

Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...

to p-hydroxy-mCPP (OH-mCPP). Caution should be exercised in coprescribing inhibitors or substrates of CYP2D6 with drugs such as Trazodone

Trazodone

Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...

and Nefazodone

Nefazodone

Nefazodone is an antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity , which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every...

that have mCPP as a metabolite.

Legal status

In Finland: Illegal
In the Netherlands: Illegal
In the United States: Legal
In Denmark: Illegal
In Germany: Illegal
In Russia: Illegal
In Sweden: Legal
In Norway: Illegal
In Brazil: Illegal
In Belgium: Illegal
In the Czech Republic: Legal

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.

Pharmacology

Pharmacokinetics

Legal status

See also