''meta''-Chlorophenylpiperazine (mCPP) is a
psychoactive drug
A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. ...
of the
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.
List phenylpiperazine derivativesAlp ...
class. It was initially developed in the late-1970s and used in
scientific research
The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...
before being sold as a
designer drug
A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. D ...
in the mid-2000s.
It has been detected in pills touted as legal alternatives to illicit
stimulants in
New Zealand
New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...
and pills sold as "
ecstasy" in
Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...
and the
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
.
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
In behavioral psychology, reinforcement is a consequence applied that will strengthen an organism's future behavior whenever that behavior is preceded by a specific antecedent stimulus. This strengthening effect may be measured as a higher freq ...
effects, but has "psychostimulant, anxiety-provoking, and hallucinogenic effects."
It is also known to produce
dysphoric,
depressive, and
anxiogenic effects in rodents and humans,
and can induce
panic attack
Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...
s 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
Antimigraine drugs are medications intended to reduce the effects or intensity of migraine headache. They include drugs for the treatment of acute migraine symptoms as well as drugs for the prevention of migraine attacks.
Treatment of acute sy ...
medications.
It has potent
anorectic
An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic.
The term is (from the Greek ''ἀν-'' (an-) = "without" a ...
effects and has encouraged the development of selective
5-HT2C receptor agonists for the treatment of
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
as well.
Pharmacology
Pharmacodynamics
mCPP possesses significant
affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Par ...
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
Net or net may refer to:
Mathematics and physics
* Net (mathematics), a filter-like topological generalization of a sequence
* Net, a linear system of divisors of dimension 2
* Net (polyhedron), an arrangement of polygons that can be folded up ...
.
It behaves as an
agonist at most serotonin receptors.
mCPP has been shown to act not only as a
serotonin reuptake inhibitor
A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to incre ...
but as a
serotonin releasing agent
A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter e ...
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 is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
,
headaches, and
appetite loss
Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...
are likely mediated by its actions on the 5-HT
2C receptor.
Other effects of mCPP include
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
hypoactivity, and
penile erection
An erection (clinically: penile erection or penile tumescence) is a physiological phenomenon in which the penis becomes firm, engorged, and enlarged. Penile erection is the result of a complex interaction of psychological, neural, vascular, ...
, the latter two the result of increased 5-HT
2C activity and the former likely via 5-HT
3 stimulation.
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).
It acts as a
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...
of the human 5-HT
2A and 5-HT
2C receptors but as an
antagonist of the human 5-HT
2B receptors.
Pharmacokinetics
mCPP is
metabolized
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
via the
CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
isoenzyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...
by
hydroxylation to ''para''-hydroxy-mCPP (''p''-OH-mCPP) and this plays a major role in its metabolism.
The
elimination half-life
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of mCPP is 4 to 14 hours.
mCPP is a
metabolite of a variety of other piperazine drugs including
trazodone
Trazodone, sold under many brand names, is an antidepressant medication. It is used to treat major depressive disorder, anxiety disorders, and difficulties with sleep. The medication is taken orally.
Common side-effects include dry mouth, f ...
,
nefazodone
Nefazodone, sold formerly under the brand names Serzone, Dutonin, and Nefadar among others, is an atypical antidepressant which was first marketed by Bristol-Myers Squibb (BMS) in 1994 but has since largely been discontinued. BMS withdrew it from ...
,
etoperidone,
enpiprazole,
mepiprazole
Mepiprazole (INN, BAN) (brand name Psigodal) is an anxiolytic drug of the phenylpiperazine group with additional antidepressant properties that is marketed in Spain. It acts as a 5-HT2A and α1-adrenergic receptor antagonist and inhibits th ...
,
cloperidone,
peraclopone, and
BRL-15,572.
It is formed by
dealkylation via
CYP3A4.
Caution should be exercised in concomitant administration of
CYP2D6
Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.
CYP2D ...
inhibitors such as
bupropion,
fluoxetine,
paroxetine
Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...
, and
thioridazine
Thioridazine (Mellaril or Melleril) is a first generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwid ...
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
Quipazine is a serotonergic drug of the piperazine group which is used in scientific research. It was originally intended as an antidepressant but never developed for medical use.
Pharmacology
Pharmacodynamics
Quipazine is a serotonin reuptake ...
,
ORG-12962
ORG-12962 is a pyridinylpiperazine drug developed by Organon, which acts as a potent and selective agonist for the 5-HT2 receptor family, with highest affinity at 5-HT2C and lowest at 5-HT2B subtypes. It was developed as a potential anti-a ...
, and
3C-PEP.
Society and culture
Legal status
Belgium
mCPP is illegal in Belgium.
Brazil
mCPP is illegal in
Brazil
Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
.
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
Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of B ...
.
Germany
mCPP is illegal in
Germany
Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
.
Hungary
mCPP is illegal in
Hungary
Hungary ( hu, Magyarország ) is a landlocked country in Central Europe. Spanning of the Pannonian Basin, Carpathian Basin, it is bordered by Slovakia to the north, Ukraine to the northeast, Romania to the east and southeast, Serbia to the ...
since 2012.
Japan
mCPP is illegal in
Japan since 2006.
Netherlands
mCPP is legal in
the Netherlands
)
, anthem = ( en, "William of Nassau")
, image_map =
, map_caption =
, subdivision_type = Sovereign state
, subdivision_name = Kingdom of the Netherlands
, established_title = Before independence
, established_date = Spanish Netherl ...
.
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. However, it is important to note that mCPP is legally used for scientific research.
Norway
mCPP is illegal in
Norway
Norway, officially the Kingdom of Norway, is a Nordic country in Northern Europe, the mainland territory of which comprises the western and northernmost portion of the Scandinavian Peninsula. The remote Arctic island of Jan Mayen and the ...
.
Russia
mCPP is illegal in
Russia
Russia (, , ), or the Russian Federation, is a transcontinental country spanning Eastern Europe and Northern Asia. It is the largest country in the world, with its internationally recognised territory covering , and encompassing one-eig ...
.
Sweden
mCPP is illegal in
Sweden.
Poland
mCPP is illegal in
Poland
Poland, officially the Republic of Poland, is a country in Central Europe. It is divided into 16 administrative provinces called voivodeships, covering an area of . Poland has a population of over 38 million and is the fifth-most populou ...
.
United States
mCPP is not scheduled at the federal level in the
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
,
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
The Federal Analogue Act, , is a section of the United States Controlled Substances Act passed in 1986 which allows any chemical "substantially similar" to a controlled substance listed in Schedule I or II to be treated as if it were listed in ...
.
However, "chlorophenylpiperazine" is a Schedule I
controlled substance
A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Single ...
in the state of
Florida
Florida is a state located in the Southeastern region of the United States. Florida is bordered to the west by the Gulf of Mexico, to the northwest by Alabama, to the north by Georgia, to the east by the Bahamas and Atlantic Ocean, and to ...
making it illegal to buy, sell, or possess in this state.
Turkey
mCPP is illegal in
Turkey
Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a transcontinental country located mainly on the Anatolian Peninsula in Western Asia, with a small portion on the Balkan Peninsula in ...
since 20/05/2009.
See also
*
Substituted piperazine
Substituted piperazines are a class of chemical compounds based on a piperazine core. Some are used as recreational drugs and some are used in scientific research.
List of substituted piperazines
Benzylpiperazines
File:Benzylpiperazine.svg, 1- ...
References
External links
*
{{DEFAULTSORT:Chlorophenylpiperazine, Meta-
5-HT2A antagonists
5-HT2B antagonists
5-HT2C agonists
Alpha-1 blockers
Alpha-2 blockers
Anxiogenics
Designer drugs
Human drug metabolites
Serotonin receptor agonists
Serotonin releasing agents
Stimulants