PMA
Encyclopedia
para-Methoxyamphetamine (PMA; "Death", "Dr. Death", "Chicken Powder", "Chicken Yellow"), also known as 4-methoxyamphetamine (4-MA), is a serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...

 drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 of the amphetamine
Substituted amphetamine
Substituted amphetamines are a chemical class of stimulants, entactogens, hallucinogens, and other drugs. They feature a phenethylamine core with a methyl group attached to the alpha carbon resulting in amphetamine, along with additional substitutions...

 class. Unlike other similar drugs of this family, PMA does not produce 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...

, euphoriant
Euphoriant
A euphoriant is a type of psychoactive drug which tends to induce feelings of euphoria, the effects of which may include relaxation, anxiolysis, stress relief, mood lift, pleasure, and a rush although these effects are not necessary for a drug to be a euphoriant. Many euphoriants are notorious for...

, or entactogen effects, and behaves more like an antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

 in comparison, though it does have some 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...

 properties.

PMA has been occasionally found in tablets labeled as MDMA (colloquially known as "ecstasy"), although its effects are markedly different compared to those of MDMA. PMA is commonly synthesized from anethole
Anethole
Anethole is a phenylpropene, a type of aromatic compound that occurs widely in nature, in essential oils...

, the flavor compound of anise
Anise
Anise , Pimpinella anisum, also called aniseed, is a flowering plant in the family Apiaceae native to the eastern Mediterranean region and Southwest Asia. Its flavor resembles that of liquorice, fennel, and tarragon.- Biology :...

 and fennel
Fennel
Fennel is a plant species in the genus Foeniculum . It is a member of the family Apiaceae . It is a hardy, perennial, umbelliferous herb, with yellow flowers and feathery leaves...

, mainly because the starting material for MDMA, safrole
Safrole
Safrole, also known as shikimol, is a phenylpropene. It is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil , or synthesized from other related methylenedioxy...

, has become less available due to law enforcement action, causing illicit drug manufacturers to use anethole as an alternative. Once thought to be a human invention, recent research suggests PMA occurs as a trace alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

 in plants including certain Acacia
Acacia berlandieri
Acacia berlandieri is a shrub native to the Southwestern United States and northeast Mexico that belongs to the subfamily Mimosoideae of Fabaceae . It grows tall, with blossoms that are spherical and white, occurring from February through April...

 species.

History

PMA first came into circulation in the early 1970s, where it was used intentionally as a substitute for the hallucinogenic properties of LSD
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...

. It went by the street names of "Chicken Powder" and "Chicken Yellow" and was found to be the cause of a number of drug overdose deaths (the dosages taken being in the range of hundreds of milligrams) in the United States and Canada from that time. Between 1974 and the mid-1990s, there appear to have been no known fatalities from PMA. Several deaths reported as MDMA-induced in Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

 in the mid-1990s are now considered to have been caused by PMA, the users unaware that they were ingesting PMA and not MDMA as they had intended. There have been a number of PMA-induced deaths around the world since then.

Distribution

Because PMA is given out through the same venues and distribution channels that MDMA tablets are, the risk of being severely injured, hospitalized or even dying from use of ecstasy increases significantly when a batch of ecstasy pills containing PMA starts to be sold in a particular area. PMA pills could be a variety of colours or imprints, and there is no way of knowing just from the appearance of a pill what drug(s) it might contain. However, it is possible to test any ecstasy pill that is bought with a pill testing
Pill testing
Pill Testing is a process used to identify substances contained within a pill, usually illicit substances.Since illicit drugs like MDMA are bought from drug dealers on the black market, both the source and contents of the substance are unknown. Pills sold by dealers as Ecstasy, may not contain the...

 kit before it is consumed to determine its content, and to monitor reported results from drug testing laboratories and avoid any pills that are reported to contain PMA. Notable batches of pills containing PMA have included Mitsubishi Turbo, Blue Transformers, Red/Blue Mitsubishi and Yellow Euro pills. Also PMA has been found in powder form.

Pharmacology

PMA acts as a potent
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

 and selective
Binding selectivity
Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate...

 serotonin releasing agent
Selective serotonin releasing agent
A selective serotonin releasing agent is a type of drug which selectively induces the release of serotonin from the pre-synaptic neuron into the synapse...

 (SSRA) with only very weak 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...

 and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

. However, relative to MDMA, it is considerably less effective as a releaser of serotonin and behaves more like 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...

 in comparison. It evokes robust hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

 in rodents while producing only modest hyperactivity and serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...

 neurotoxicity
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

, substantially lower than that caused by MDMA, and only at very high doses. Accordingly, it is not self-administered
Self-administration
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to him-, her-, or itself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient....

 by rodents unlike amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

 and MDMA, and anecdotal reports by humans suggest it is not particularly euphoric
Euphoriant
A euphoriant is a type of psychoactive drug which tends to induce feelings of euphoria, the effects of which may include relaxation, anxiolysis, stress relief, mood lift, pleasure, and a rush although these effects are not necessary for a drug to be a euphoriant. Many euphoriants are notorious for...

 at all, perhaps even dysphoric in contrast. PMA has also been shown to act as a potent, reversible inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

 of the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 MAO-A with no significant effects on MAO-B, and the combination of this property and serotonin release is likely responsible for its high lethality
Lethality
Lethality is a term designating the ability of a weapon to kill. Most often this term is used when referring to chemical weapons, biological weapons, or their chemical components. The use of this term denotes the ability of these weapons to kill, but also the possibility that they may not kill...

 potential.

It appears that PMA elevates body temperatures dramatically; the cause of this property is suspected to be related to its ability to inhibit MAO-A and at the same time releasing large amounts of serotonin, effectively causing serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...

. Amphetamines, especially serotonergic analogues such as MDMA, are strongly contraindicated
Contraindication
In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...

 to take with MAOIs. Many amphetamines and adrenergic compounds raise body temperatures; whereas some tend to produce more euphoric activity, or peripheral vasoconstriction, or tend to favor one effect over another, it appears that PMA activates the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 much more strongly than MDMA and other drugs like ephedrine, thereby causing rapid increases in body temperature (which is the major cause of death in PMA mortalities). Many people taking PMA try to get rid of the heat by taking off their clothes, taking cold showers or wrapping themselves in wet towels, and even sometimes by shaving off their hair.

Dangers

PMA has been associated with numerous adverse reactions including death. Effects of PMA ingestion include many effects of the hallucinogenic amphetamines including accelerated
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

 and irregular heartbeat, blurred vision, and a strong feeling of intoxication that is often unpleasant. While PMA can reportedly be euphoric at low doses, the dose-response curve is much steeper than that of MDMA, and at higher doses unpleasant effects such as 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
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, severe hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

 and hallucinations quickly overpower any pleasurable effects. The effects of PMA also seem to be much more unpredictable and variable between individuals than those of MDMA, and sensitive individuals may die from a dose of PMA that a less susceptible person might only be mildly affected by. There are approximately twice as many deaths caused by PMA as by MDMA, even though the actual proportion of PMA on the market is only a fraction of that of MDMA. While PMA alone may cause significant toxicity, the combination of PMA with MDMA has a synergistic effect that seems to be particularly hazardous. Since PMA has a slow onset of effects, several deaths have occurred where individuals have taken a pill containing PMA, followed by a pill containing MDMA some time afterwards due to thinking that the first pill was not active.

Treatment of overdose

PMA overdose can be a serious medical emergency that may occur at only slightly above the usual recreational dose range, especially if PMA is mixed with other stimulant drugs such as cocaine or MDMA. Characteristic symptoms are pronounced hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, along with agitation, confusion, and convulsion
Convulsion
A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...

s. PMA overdose also tends to cause hypoglycaemia and hyperkalaemia, which can help to distinguish it from MDMA overdose. Complications can sometimes include more serious symptoms such as rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...

 and cerebral hemorrhage, requiring emergency surgery. There is no specific antidote, so treatment is symptomatic, and usually includes both external cooling, and internal cooling via IV infusion of cooled saline. Benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...

s are used initially to control convulsions, with stronger anticonvulsants such as phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...

 or thiopental used if convulsions continue. Blood pressure can be lowered either with a combination of alpha blocker
Alpha blocker
Alpha-1 blockers constitute a variety of drugs which block α1-adrenergic receptors in arteries and smooth muscles.-Pharmacology:...

s and beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...

s (or a mixed alpha/beta blocker), or with other drugs such as nifedipine
Nifedipine
Nifedipine is a dihydropyridine calcium channel blocker...

 or nitroprusside. Serotonin antagonist
Serotonin antagonist
A serotonin antagonist is a drug used to inhibit the action at serotonin receptors.Many of the most important medications of this class selectively act at the 5-HT3 receptor, and thus are known as 5-HT3 antagonists...

s and dantrolene
Dantrolene
Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia...

 may be used as required. Despite the seriousness of the condition, the majority of patients survive if treatment is given in time, however patients with a core body temperature over 40°C at presentation tend to have a poor prognosis.

Analogues

Four analogues of PMA have been reported to be sold on the black market, including PMMA
Paramethoxymethamphetamine
para-Methoxymethamphetamine , is a stimulant drug related to para-methoxyamphetamine .PMMA reputedly produces similar effects to PMA, but is apparently slightly more similar to MDMA in effects and has slightly less tendency to produce severe hyperthermia, at least at low doses...

, PMEA
Paramethoxyethylamphetamine
para-Methoxyethylamphetamine , is a stimulant drug related to PMA. PMEA reputedly produces similar effects to PMA, but is considerably less potent and seems to have slightly less tendency to produce severe hyperthermia, at least at low doses...

, 4-ETA and 4-MTA. These are the N-methyl, N-ethyl, 4-ethoxy and 4-methylthio analogues of PMA, respectively. PMMA and PMEA are reportedly weaker, more "ecstasy-like" and somewhat less dangerous than PMA itself, but can still produce nausea and hyperthermia similar to that produced by PMA, albeit at slightly higher doses. 4-EtOA was briefly sold in Canada in the 1970s, but little is known about it. 4-MTA, however, is even more dangerous than PMA and produces strong serotonergic effects and intense hyperthermia, but with little to no euphoria, and was implicated in several deaths in the late 1990s.

Legality

It is classified as a Schedule I hallucinogen
Psychedelics, dissociatives and deliriants
This general group of pharmacological agents can be divided into three broad categories: psychedelics, dissociatives, and deliriants. These classes of psychoactive drugs have in common that they can cause subjective changes in perception, thought, emotion and consciousness...

 under the Controlled Substances Act
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

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

. Internationally, PMA is a Schedule I drug under the Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...

.

See also

  • 1-Aminomethyl-5-methoxyindane
    1-Aminomethyl-5-methoxyindane
    1-Aminomethyl-5-methoxyindane , is a drug developed by a team led by David E. Nichols at Purdue University, which acts as a selective serotonin releasing agent and binds to the serotonin transporter with similar affinity to DFMDA....

     (AMMI)
  • 2-Methoxyamphetamine
    2-Methoxyamphetamine
    2-Methoxyamphetamine , also known as ortho-methoxyamphetamine , is a drug of the amphetamine class. It is substantially weaker in inhibiting the reuptake of and inducing the release of the monoamine neurotransmitters compared to related agents such as amphetamine, MMA, and PMA, and may instead act...

     (OMA)
  • 3-Methoxyamphetamine
    3-Methoxyamphetamine
    meta-Methoxyamphetamine , also known as 3-methoxyamphetamine , is a stimulant drug from the amphetamine family...

     (MMA)
  • 4-Methylamphetamine
    4-Methylamphetamine
    4-Methylamphetamine is a stimulant and anorectic drug of the phenethylamine and amphetamine chemical classes....

     (4-MA)
  • 4-Ethoxyamphetamine (4-ETA)
  • 4-Methylthioamphetamine (4-MTA)
  • 4-Methoxy-N-ethylamphetamine (PMEA)
  • 4-Methoxy-N-methylamphetamine (PMMA)

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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