Trifluoromethylphenylpiperazine
Encyclopedia
3-Trifluoromethylphenylpiperazine (TFMPP) is a recreational drug of the piperazine
chemical class. Usually in combination with its analogue benzylpiperazine
(BZP), it is sold as a legal alternative to the illicit drug MDMA ("Ecstasy") under the name "Legal X".
s, and functions as a full agonist at all sites except the 5-HT2A receptor, where it acts as a weak partial agonist
or antagonist
. Unlike the related piperazine compound meta-chlorophenylpiperazine (mCPP), TFMPP has insignificant affinity for the 5-HT3 receptor (IC50 = 2,373 nM). TFMPP also binds to the SERT
(EC50 = 121 nM) and evokes the release
of serotonin
. It has no effects on dopamine
or norepinephrine
reuptake
or efflux.
The dosage commonly used when combined with BZP for "ecstasy-like effects" is between 30 and 100 mg, while higher doses of TFMPP alone cause mildly hallucinogenic effects at around 100–250 mg; however, higher doses can cause a range of side effects including migraine
headaches, muscle aches, nausea
and vomiting, as well as a come-down syndrome characterized by insomnia
, loss of appetite, and headache
(see below). These side effects tend to discourage use of TFMPP.
, anxiety
, nausea
and vomiting, headaches and muscle aches which may resemble migraine
, seizures, impotence, and rarely psychosis
, as well as a prolonged and unpleasant hangover effect similar to that produced by alcohol. These side effects tend to be significantly worsened when the BZP/TFMPP mix is consumed alongside alcohol
, especially the headache, nausea, and hangover.
However, it is difficult to say how many of these side effects are produced by TFMPP itself, as it has rarely been marketed without BZP also being present, and all of the side effects mentioned are also produced by BZP (which has been sold as a single drug). Studies into other related piperazine drugs such as mCPP
suggest that certain side effects such as anxiety
, headache
and nausea
are common to all drugs of this class, and pills containing TFMPP are reported by users to produce comparatively more severe hangover effects than those containing only BZP. The drug can also cause the body to tremble for a long period of time.
As of December 3, 2005, TFMPP is illegal in Denmark. As of March 1, 2006, TFMPP is scheduled as a "dangerous substance" in Sweden. TFMPP is unscheduled in the Netherlands
. TFMPP was briefly emergency scheduled in Schedule I in the USA, but the scheduling expired in April 2004 and has not been renewed. Therefore, unlike its cousin benzylpiperazine
, TFMPP is not currently an illicit drug under United States federal law. However, some states have banned the drug in their criminal statutes making its possession a felony.
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.
As of December 2009 TFMPP has been made a Class C drug in the UK along with BZP.
Piperazine
Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste....
chemical class. Usually in combination with its analogue benzylpiperazine
Benzylpiperazine
Benzylpiperazine is a recreational drug with euphoric, stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. Adverse effects have been reported following its use including acute psychosis, renal toxicity, and seizures...
(BZP), it is sold as a legal alternative to the illicit drug MDMA ("Ecstasy") under the name "Legal X".
Pharmacology
TFMPP has affinity for the 5-HT1A (Ki = 288 nM), 5-HT1B (Ki = 132 nM), 5-HT1D (Ki = 282 nM), 5-HT2A (Ki = 269 nM), and 5-HT2C (Ki = 62 nM) receptorReceptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s, and functions as a full agonist at all sites except the 5-HT2A receptor, where it acts as a weak partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
or antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
. Unlike the related piperazine compound meta-chlorophenylpiperazine (mCPP), TFMPP has insignificant affinity for the 5-HT3 receptor (IC50 = 2,373 nM). TFMPP also binds to 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...
(EC50 = 121 nM) and evokes the release
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...
of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
. It has no effects on dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
or norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
reuptake
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
or efflux.
Use and effects
TFMPP is rarely used by itself. In fact, TFMPP reduces locomotor activity and produces aversive effects in animals rather than self-administration, which probably explains the decision of the DEA not to permanently make TFMPP a controlled substance. More commonly, TFMPP is co-administered with BZP, which acts as a norepinephrine and dopamine releasing agent. Due to the serotonin agonist effects and increase in serotonin, norepinephrine, and dopamine levels produced by the BZP/TFMPP combination, this mixture of drugs produces effects which crudely mimic those of MDMA.The dosage commonly used when combined with BZP for "ecstasy-like effects" is between 30 and 100 mg, while higher doses of TFMPP alone cause mildly hallucinogenic effects at around 100–250 mg; however, higher doses can cause a range of side effects including migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
headaches, muscle aches, 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...
and vomiting, as well as a come-down syndrome characterized by insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, loss of appetite, and 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...
(see below). These side effects tend to discourage use of TFMPP.
Side effects
The combination of BZP and TFMPP has been associated with a range of side effects, including insomniaInsomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, 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,...
, 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...
and vomiting, headaches and muscle aches which may resemble migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
, seizures, impotence, and rarely psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, as well as a prolonged and unpleasant hangover effect similar to that produced by alcohol. These side effects tend to be significantly worsened when the BZP/TFMPP mix is consumed alongside alcohol
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
, especially the headache, nausea, and hangover.
However, it is difficult to say how many of these side effects are produced by TFMPP itself, as it has rarely been marketed without BZP also being present, and all of the side effects mentioned are also produced by BZP (which has been sold as a single drug). Studies into other related piperazine drugs such as mCPP
1-(3-Chlorophenyl)piperazine
meta-Chlorophenylpiperazine 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...
suggest that certain side 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
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...
and 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...
are common to all drugs of this class, and pills containing TFMPP are reported by users to produce comparatively more severe hangover effects than those containing only BZP. The drug can also cause the body to tremble for a long period of time.
Legal status
Netherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
. TFMPP was briefly emergency scheduled in Schedule I in the USA, but the scheduling expired in April 2004 and has not been renewed. Therefore, unlike its cousin benzylpiperazine
Benzylpiperazine
Benzylpiperazine is a recreational drug with euphoric, stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. Adverse effects have been reported following its use including acute psychosis, renal toxicity, and seizures...
, TFMPP is not currently an illicit drug under United States federal law. However, some states have banned the drug in their criminal statutes making its possession a felony.
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.
As of December 2009 TFMPP has been made a Class C drug in the UK along with BZP.
See also
- 1-(4-(Trifluoromethyl)phenyl)piperazine1-(4-(Trifluoromethyl)phenyl)piperazine1-piperazine is a serotonergic releasing agent. It is rarely encountered as a designer drug but is much less common than the "normal" isomer meta-TFMPP.-References:...
(pTFMPP) - 1-Benzylpiperazine (BZP)
- 1-Methyl-4-benzylpiperazine1-Methyl-4-benzylpiperazineMBZP is a stimulant drug which is a derivative of benzylpiperazine. MBZP has been sold as an ingredient in legal recreational drugs known as "Party pills", initially in New Zealand and subsequently in other countries around the world.The effects of MBZP are very similar to those of BZP, but the...
(MBZP) - 1,4-Dibenzylpiperazine (DBZP)
- 3-Chlorophenylpiperazine1-(3-Chlorophenyl)piperazinemeta-Chlorophenylpiperazine 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...
(mCPP) - 3,4-Methylenedioxy-1-benzylpiperazine (MDBZP)
- 4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP)
- 4-FluorophenylpiperazinePFPPpara-Fluorophenylpiperazine is a piperazine derivative with mildly psychedelic and euphoriant effects...
(pFPP) - 4-MethoxyphenylpiperazineMeOPPpara-Methoxyphenylpiperazine is a piperazine derivative with stimulant effects which has been sold as an ingredient in "Party pills", initially in New Zealand and subsequently in other countries around the world.MeOPP has been found in vitro to inhibit the reuptake and induce the release of the...
(MeOPP) - Org 12,962Org 12,962Org 12,962 is a 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...