Monoamine oxidase inhibitor - AbsoluteAstronomy.com

Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drug

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;...

s prescribed for the treatment of depression

Clinical depression

Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

. They are particularly effective in treating atypical depression

Atypical depression

Atypical depression is a subtype of dysthymia and major depression, sharing many of the symptoms of both, but also being characterized by mood reactivity—being able to experience improved mood in response to positive events. In contrast, sufferers of "melancholic" depression generally cannot...

.

Because of potentially lethal dietary and drug interactions, monoamine oxidase

Monoamine oxidase

L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...

inhibitors have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitor

Selective serotonin reuptake inhibitor

Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

s and tricyclic antidepressants) have failed. However, a transdermal patch form of the MAOI selegiline

Selegiline

Selegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...

, called Emsam

Emsam

Emsam is the trade name of an antidepressant of the monoamine oxidase inhibitor class. Emsam is a transdermal patch containing the MAOI selegiline. Selegiline, in small doses, is most commonly used in the treatment of Parkinson's disease. It is also effective in higher doses for the treatment...

, was approved for use by the Food and Drug Administration

Food and Drug Administration

The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

in the United States

United States

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

on February 28, 2006.

Indications

In the past, MAOIs were prescribed for those resistant to tricyclic antidepressant

Tricyclic antidepressant

Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...

therapy, but newer reversible MAOIs such as selegiline

Selegiline

and moclobemide

Moclobemide

Moclobemide is a monoamine oxidase inhibitor drug primarily used to treat depression and social anxiety. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States...

provide a safer alternative and are now sometimes used as first-line therapy, although these substances are not always as effective as their predecessors.

MAOI's have been found to be effective in the treatment of panic disorder

Panic disorder

Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...

with agoraphobia

Agoraphobia

Agoraphobia is an anxiety disorder defined as a morbid fear of having a panic attack or panic-like symptoms in a situation from which it is perceived to be difficult to escape. These situations can include, but are not limited to, wide-open spaces, crowds, or uncontrolled social conditions...

, social phobia

Social phobia

Social phobia may refer to any of the following conditions:* Social anxiety disorder – a diagnosis referring to clinically excessive social anxiety...

, atypical depression

Atypical depression

or mixed 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,...

and depression, bulimia, posttraumatic stress disorder as well as borderline personality disorder

Borderline personality disorder

Borderline personality disorder is a personality disorder described as a prolonged disturbance of personality function in a person , characterized by depth and variability of moods.The disorder typically involves unusual levels of instability in mood; black and white thinking, or splitting; the...

. There are reports of MAOI efficacy in obsessive-compulsive disorder

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...

(OCD), trichotillomania

Trichotillomania

Trichotillomania, which is classified as an impulse control disorder by DSM-IV, is the compulsive urge to pull out one's own hair leading to noticeable hair loss, distress, and social or functional impairment. It is often chronic and difficult to treat....

, dysmorphophobia and avoidant personality disorder

Avoidant personality disorder

Avoidant personality disorder is a personality disorder recognized in the Diagnostic and Statistical Manual of Mental Disorders handbook in a person characterized by a pervasive pattern of social inhibition, feelings of inadequacy, extreme sensitivity to negative evaluation, and avoidance of...

; however these reports are from uncontrolled case reports.

MAOIs can also be used in the treatment of Parkinson's disease

Parkinson's disease

Parkinson's disease is a degenerative disorder of the central nervous system...

by targeting MAO-B in particular (therefore affecting dopaminergic neurons), as well as providing an alternative for migraine

Migraine

Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...

prophylaxis. Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression

Clinical depression

Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

and anxiety

Anxiety

.

MAOIs appear to be particularly indicated for out- patients with "neurotic depression" complicated by panic disorder or hysteroid dysphoria

Hysteroid dysphoria

Hysteroid dysphoria is a name given to repeated episodes of depressed mood in response to feeling rejected, and a craving for sweets, especially chocolate....

, which involves repeated episodes of depressed mood in response to feeling rejected.

Mode of action

MAOIs act by inhibiting the activity of monoamine oxidase

Monoamine oxidase

, thus preventing the breakdown of monoamine neurotransmitter

Monoamine neurotransmitter

thumb|right|350px| A phylogenetic tree showing how a number of monoamine receptors are related to each other.Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group that is connected to an aromatic ring by a two-carbon chain...

s and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates

Deamination

Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases.In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are...

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...

, melatonin

Melatonin

Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...

, epinephrine

Epinephrine

Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

and norepinephrine

Norepinephrine

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

. MAO-B preferentially deaminates phenylethylamine and trace amine

Trace amine

Trace amines are endogenous compounds structurally related to classical biogenic amines, such as catecholamines, serotonin and histamine. Trace amines include p-tyramine, β-phenylethylamine, tryptamine, octopamine, and 3-iodothyronamine, and are found in the nervous systems of animals from insects...

s. 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...

is equally deaminated by both types. Many formulations have forms of fluoride

Fluoride

Fluoride is the anion F−, the reduced form of fluorine when as an ion and when bonded to another element. Both organofluorine compounds and inorganic fluorine containing compounds are called fluorides. Fluoride, like other halides, is a monovalent ion . Its compounds often have properties that are...

attached to assist in permeating the blood-brain barrier

Blood-brain barrier

The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

, which is suspected as a factor in pineal gland

Pineal gland

The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...

effects.

Reversibility

The early MAOIs inhibited monoamine oxidase irreversibly. When they react with monoamine oxidase, they permanently deactivate it, and the enzyme cannot function until it has been replaced by the body, which can take about two weeks. A few newer MAOIs, notably moclobemide

Moclobemide

, are reversible, meaning that they are able to detach from the enzyme to facilitate usual catabolism

Catabolism

Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...

of the substrate

Substrate (biochemistry)

In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

. The level of inhibition in this way is governed by the concentrations of the substrate and the MAOI.

Harmaline

Harmaline

Harmaline is a fluorescent psychoactive indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the reduced hydrogenated form of harmine.-Occurrence in nature:...

found in Peganum harmala, as well as the Ayahuasca vine, Banisteriopsis caapi
Banisteriopsis caapi
Banisteriopsis caapi, also known as Ayahuasca, Caapi or Yage, is a South American jungle vine of the family Malpighiaceae. It is used to prepare Ayahuasca, a decoction that has a long history of entheogenic uses as a medicine and "plant teacher" among the indigenous peoples of the Amazon Rainforest...

and tobacco

Tobacco

Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...

is a reversible inhibitor of MAO-A (RIMA

Rima

Rima, also known as Rima the Jungle Girl, is the fictional heroine of W. H. Hudson's 1904 novel Green Mansions: A Romance of the Tropical Forest. In 1974, she was adapted into a comic book character and featured in the short-lived monthly series Rima the Jungle Girl, published by DC Comics...

Selectivity

In addition to reversibility, MAOIs differ by their selectivity of the MAO receptor. Some MAOIs inhibit both MAO-A and MAO-B equally, other MAOIs have been developed to target one over the other.

MAO-A inhibition reduces the breakdown of primarily serotonin

Serotonin

, epinephrine

Epinephrine

, and norepinephrine

Norepinephrine

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

and thus has a higher risk of 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...

and/or a hypertensive crisis. Tyramine

Tyramine

Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...

is broken down by MAO-A (and MAO-B), therefore inhibiting its action may result in excessive build-up of it, so diet must be monitored for tyramine intake.

MAO-B inhibition reduces the breakdown mainly of dopamine

Dopamine

and phenethylamine

Phenethylamine

Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

so there are no dietary restrictions associated with this. MAO-B would also metabolize tyramine, as the only differences dopamine, phenethylamine, and tyramine are two phenylhydroxyl groups on carbons 3 and 4. The 4-OH would not be a steric hindrance to MAO-B on tyramine. Two MAO-Bi drugs, selegiline

Selegiline

and rasagiline

Rasagiline

Rasagiline is an irreversible inhibitor of monoamine oxidase used as a monotherapy in early Parkinson's disease or as an adjunct therapy in more advanced cases. It is selective for MAO type B over type A by a factor of fourteen....

have been approved by the FDA without dietary restrictions, except in high dosage treatment where they lose their selectivity.

Dangers

When ingested orally, MAOIs inhibit the catabolism

Catabolism

of dietary amines. When foods containing tyramine

Tyramine

Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...

are consumed (so-called "cheese effect"), the individual may suffer from hypertensive crisis. If foods containing tryptophan

Tryptophan

Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

are consumed, hyperserotonemia

Serotonin syndrome

may result. The amount required to cause a reaction varies greatly from individual to individual, and depends on the degree of inhibition, which in turn depends on dosage and selectivity.

The exact mechanism by which tyramine causes a hypertensive reaction is not well understood, but it is assumed that tyramine displaces norepinephrine from the storage vesicles. This may trigger a cascade in which excessive amounts of norepinephrine can lead to a hypertensive crisis. Another theory suggests that proliferation and accumulation of catecholamines causes hypertensive crisis

Tyrosine

Tyrosine

Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

is the precursor to catecholamines, not tyramine. Tyramine is a breakdown product of tyrosine. In the gut and during fermentation tyrosine, an amino acid, is decarboxylated

Decarboxylation

Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...

to tyramine. Ordinarily, tyramine is deaminated in the liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

to an inactive metabolite, but when the hepatic MAO (primarily MAO-A) is inhibited, the "first-pass" clearance of tyramine is blocked and circulating tyramine levels can climb. Elevated tyramine competes with tyrosine for transport across the blood-brain barrier (via aromatic amino acid transport) where it can then enter adrenergic nerve terminals

Adrenergic receptor

The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....

. Once in the cytoplasm

Cytoplasm

The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

ic space, tyramine will be transported via the vesicular monoamine transporter

Vesicular monoamine transporter

The vesicular monoamine transporter is a transport protein integrated into the membrane of intracellular vesicles of presynaptic neurons. It acts to transport monoamines into the synaptic vesicles.-Monoamines:...

(VMAT) into synaptic vesicles thereby displacing norepinephrine. The mass transfer of norepinephrine from its vesicular storage space into the extracellular space via mass action can precipitate the hypertensive crisis. Hypertensive crises can sometimes result in stroke or cardiac arrhythmia if not treated. This risk is generally not present with RIMA

Rima

s. Both kinds of intestinal MAO inhibition can cause hyperpyrexia, nausea, and 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"...

if foods high in levodopa

Levodopa

L-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...

are consumed.

Examples of foods and drinks with potentially high levels of tyramine

Tyramine

Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...

include liver

Liver (food)

The liver of mammals, fowl, and fish are commonly eaten as food by humans. Domestic pig, ox, lamb, calf, chicken, and goose livers are widely available from butchers and supermarkets....

and fermented substances, such as alcoholic beverages and aged cheese

Cheese

Cheese is a generic term for a diverse group of milk-based food products. Cheese is produced throughout the world in wide-ranging flavors, textures, and forms....

s. (See a list of foods containing tyramine). Examples of levodopa-containing foods include broad beans

Vicia faba

This article refers to the Broad Bean plant. For Broadbean the company, see Broadbean, Inc.Vicia faba, the Broad Bean, Fava Bean, Field Bean, Bell Bean or Tic Bean, is a species of bean native to north Africa and southwest Asia, and extensively cultivated elsewhere. A variety is provisionally...

. These diet restrictions are not necessary for those taking selective MAO-B inhibitors, unless these are being taken in high dosages, as mentioned above.

It deserves separate mention that some meat extracts and yeast extracts (Bovril

Bovril

Bovril is the trademarked name of a thick, salty meat extract, developed in the 1870s by John Lawson Johnston and sold in a distinctive, bulbous jar. It is made in Burton upon Trent, Staffordshire, owned and distributed by Unilever UK....

, Marmite

Marmite

Marmite is the name given to two similar food spreads: the original British version, first produced in the United Kingdom and later South Africa, and a version produced in New Zealand...

, Vegemite

Vegemite

Vegemite is a dark brown Australian food paste made from yeast extract. It is a spread for sandwiches, toast, crumpets and cracker biscuits, and filling for pastries...

) contain extremely high levels of tyramine, and should not be used with these medications.

When MAOIs were first introduced, these risks were not known, and over the following four decades, fewer than 100 people have died from hypertensive crisis. Presumably due to the sudden onset and violent appearance of the reaction, MAOIs gained a reputation for being so dangerous that, for a while, they were taken off the market in America entirely. It is now known that, used as directed under the care of a qualified psychiatrist, this class of drugs remains a safe alternative for intermediate- to long-term use.

The most significant risk associated with the use of MAOIs, is the potential for interactions with over-the-counter and prescription medicines, illicit drugs or medications, and some supplements (e.g. St. John's Wort). It is vital that a doctor supervise such combinations to avoid adverse reactions. For this reason, many users carry an MAOI-card, which lets emergency medical personnel know what drugs to avoid. (E.g. adrenaline dosage should be reduced by 75%, and duration is extended.)
The risk of MAOI medications interacting with other drugs or certain foods is particularly dangerous because those on the medication who would have to restrict their diets often are depressed patients who "don't care if they live or die."

MAOIs should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, both legal and illegal etc.) except under expert care. Certain combinations can cause lethal reactions, common examples including SSRI

Selective serotonin reuptake inhibitor

s, tricyclic

Tricyclic antidepressant

s, MDMA, meperidine, tramadol

Tramadol

Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...

, and dextromethorphan

Dextromethorphan

Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...

. Agents with actions on epinephrine, norepinephrine or dopamine must be administered at much lower doses due to potentiation and prolonged effect.

Nicotine

Nicotine

Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...

, a substance frequently implicated in tobacco

Tobacco

Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...

addiction, has been shown to have "relatively weak" addictive properties when administered alone. The addictive potential increases dramatically after co-administration of an MAOI, which specifically causes sensitization

Sensitization

Sensitization is an example of non-associative learning in which the progressive amplification of a response follows repeated administrations of a stimulus. An everyday example of this mechanism is the repeated tonic stimulation of peripheral nerves that will occur if a person rubs his arm...

of the locomotor

Locomotor system

Locomotor system may mean:* Animal locomotion system* Human musculoskeletal system, also known simply as "the locomotor system"...

response in rats, a measure of addictive potential. This may be reflected in the difficulty of smoking cessation

Smoking cessation

Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...

, as tobacco

Tobacco

Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...

contains a naturally-occurring MAOI in addition to the nicotine.

Withdrawal

Antidepressants including MAOIs have some dependence

Substance dependence

The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...

producing effects, most notably a withdrawal syndrome

Withdrawal syndrome

A withdrawal syndrome, also called a discontinuation syndrome, occurs when a person suddenly stops taking or reduces the dosage of some types of medications...

, which may be severe especially if MAOIs are discontinued abruptly or over-rapidly. However, the dependence producing potential of MAOIs or antidepressants in general is not as significant as benzodiazepines. For example, antidepressants have significantly less abuse

Drug abuse

Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...

potential than benzodiazepines. Withdrawal symptoms can be managed by a gradual reduction in dosage over a period of weeks or months to minimize or prevent withdrawal symptoms.

MAOIs, as with any antidepressant medications, do not alter the course of the disorder, so it is possible that discontinuation can return the patient to the pre-treatment state.

This consideration greatly complicates switching a patient between a MAOI and a SSRI, because it is necessary to clear the system completely of one drug before starting another. If one also tapers dosage gradually, the result is that for weeks a depressed patient will have to bear the depression without chemical help during the drug-free interval. This may be preferable to risking the effects of an interaction between the two drugs, but it is often not easy.

Interactions

The MAOIs are infamous for their numerous drug interactions. Unless the interaction is desired, any drug that falls within the following classifications should be avoided:

Substances that are metabolized by monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...

as they can be boosted by up to several fold.
Substances that increase serotonin, norepinephrine, and/or dopamine activity, as too much of any of these neurochemicals can result in severe acute consequences, including 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...

, hypertensive crisis, and 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"...

, respectively.

Such substances include:

Phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

s: 2C-B
2C-B
2C-B or 4-bromo-2,5-dimethoxyphenethylamine is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin in 1974. In Shulgin's book PiHKAL, the dosage range is listed as 16–24 mg. 2C-B is sold as a white powder sometimes pressed in tablets or gel caps and is referred...

, Mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

, Phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

(PEA), etc.
- 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,...
  
  s: 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,...
  
  , MDMA ("Ecstasy"), Dextroamphetamine
  Dextroamphetamine
  Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
  
  , Methamphetamine
  Methamphetamine
  Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
  
  , DOM
  2,5-Dimethoxy-4-methylamphetamine
  2,5-Dimethoxy-4-methylamphetamine is a psychedelic and a substituted amphetamine...
  
  , etc.
Tryptamine
Tryptamine
Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...

s: DMT
Dimethyltryptamine
N,N-Dimethyltryptamine is a naturally occurring psychedelic compound of the tryptamine family. DMT is found in several plants, and also in trace amounts in humans and other mammals, where it is originally derived from the essential amino acid tryptophan, and ultimately produced by the enzyme INMT...

, Psilocin
Psilocin
Psilocin , an aromatic compound, sometimes also spelled psilocine, psilocyn, or psilotsin, is a psychedelic mushroom alkaloid. It is found in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin...

/Psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

("Magic Mushrooms"), etc.
- Lysergamides: Ergoline
  Ergoline
  Ergoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs . Ergoline derivatives are used clinically for the purpose of vasoconstriction and in the treatment of migraines and Parkinson's disease...
  
  s/LSA, 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...
  
  ("Acid"), etc.
Serotonin, Norepinephrine
Norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...

, and/or Dopamine
Dopamine reuptake inhibitor
A dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...

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...

s:
- Selective Serotonin Reuptake Inhibitor
  Selective serotonin reuptake inhibitor
  Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
  
  s (SSRIs): Citalopram
  Citalopram
  Citalopram brand names: Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor class. It has U.S...
  
  , Dapoxetine
  Dapoxetine
  Dapoxetine is a short-acting selective serotonin reuptake inhibitor marketed for the treatment of premature ejaculation in men. Dapoxetine is the only drug with regulatory approval for such an indication. Currently, it is approved in several European countries, including Finland, Sweden,...
  
  , Escitalopram
  Escitalopram
  Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is approved by the U.S...
  
  , Fluoxetine
  Fluoxetine
  Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
  
  , Fluvoxamine
  Fluvoxamine
  Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...
  
  , Paroxetine
  Paroxetine
  Paroxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline...
  
  , Sertraline
  Sertraline
  Sertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...
  
  .
- Serotonin-Norepinephrine Reuptake Inhibitor
  Serotonin-norepinephrine reuptake inhibitor
  Serotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders...
  
  s (SNRIs): Desvenlafaxine
  Desvenlafaxine
  Desvenlafaxine , also known as O-desmethylvenlafaxine, is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class developed and marketed by Wyeth . Desvenlafaxine is a synthetic form of the major active metabolite of venlafaxine...
  
  , Duloxetine
  Duloxetine
  Duloxetine is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and has been shown to be as effective as venlafaxine for generalized anxiety disorder...
  
  , Milnacipran
  Milnacipran
  Milnacipran is a serotonin–norepinephrine reuptake inhibitor used in the clinical treatment of fibromyalgia...
  
  , Venlafaxine
  Venlafaxine
  Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...
  
  .
- Norepinephrine-Dopamine Reuptake Inhibitor
  Norepinephrine-dopamine reuptake inhibitor
  A norepinephrine-dopamine reuptake inhibitor is a drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter and the dopamine transporter , respectively...
  
  s (NDRIs): Amineptine
  Amineptine
  Amineptine was developed by the French Society of Medical research in the 1960s. Under the trade-names is used as an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting...
  
  , Bupropion
  Bupropion
  Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
  
  , Methylphenidate
  Methylphenidate
  Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
  
  , Nomifensine
  Nomifensine
  Nomifensine is a norepinephrine-dopamine reuptake inhibitor developed by a team at Hoechst AG in the 1960s.. The drug was test-marketed in the United States by Hoechst AG , i.e. a drug that increases the amount of synaptic norepinephrine and dopamine available to receptors by blocking the dopamine...
  
  .
- Norepinephrine Reuptake Inhibitor
  Norepinephrine reuptake inhibitor
  A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
  
  s (NRIs): Atomoxetine, Mazindol
  Mazindol
  Mazindol is a stimulant drug of the tetracyclic chemical class which is used as an anorectic. It was developed by Sandoz-Wander in the 1960s- Indications :...
  
  , Reboxetine
  Reboxetine
  Reboxetine is a drug marketed as an antidepressant for use in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia . Its mesylate salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra...
  
  .
- Tricyclic Antidepressant
  Tricyclic antidepressant
  Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
  
  s (TCAs): Amitriptyline
  Amitriptyline
  Amitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...
  
  , Butriptyline
  Butriptyline
  Butriptyline is a tricyclic antidepressant which has been used in Europe since 1974...
  
  , Clomipramine
  Clomipramine
  Clomipramine is a tricyclic antidepressant . It was developed in the 1960s by the Swiss drug manufacturer Geigy and has been in clinical use worldwide ever since.- Indications :...
  
  , Desipramine
  Desipramine
  Desipramine is a tricyclic antidepressant . It inhibits the reuptake of norepinephrine and to a lesser extent serotonin. It is used to treat depression, but not considered a first line treatment since the introduction of SSRI antidepressants...
  
  , Dosulepin, Doxepin
  Doxepin
  Doxepin is a psychotropic agent with tricyclic antidepressant and anxiolytic properties, known under many brand-names such as Aponal, the original preparation by Boehringer-Mannheim, now part of the Roche group; Adapine, Doxal , Deptran, Sinquan and Sinequan...
  
  , Imipramine
  Imipramine
  Imipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group...
  
  , Lofepramine
  Lofepramine
  Lofepramine is a third Generation tricyclic antidepressant which was introduced in 1983 for the treatment of depressive disorders. It is partially converted to its active metabolite desipramine in vivo...
  
  , Nortriptyline
  Nortriptyline
  Nortriptyline is a second-generation tricyclic antidepressant marketed as the hydrochloride salt under the trade names Sensoval, Aventyl, Pamelor, Norpress, Allegron, Noritren and Nortrilen. It is used in the treatment of major depression and childhood nocturnal enuresis...
  
  , Protriptyline
  Protriptyline
  Protriptyline is a tricyclic antidepressant , specifically a secondary amine, indicated for the treatment of depression and ADHD...
  
  , Trimipramine
  Trimipramine
  Trimipramine is a tricyclic antidepressant . It has antidepressant, anxiolytic, antipsychotic, sedative, and analgesic effects.- Indications :...
  
  .
- Tetracyclic Antidepressant
  Tetracyclic antidepressant
  Tetracyclic antidepressants are a class of drugs used primarily as antidepressants that were first introduced in the 1970s. They are named after their chemical structure which contains four rings of atoms and are closely related to the tricyclic antidepressants which contain three rings of...
  
  s (TeCAs): Amoxapine
  Amoxapine
  Amoxapine is a tetracyclic antidepressant of the dibenzoxazepine family, though it is often classified as a secondary amine tricyclic antidepressant.- Uses :...
  
  , Maprotiline
  Maprotiline
  Maprotiline is a tetracyclic antidepressant . It is a strong norepinephrine reuptake inhibitor with only weak effects on serotonin and dopamine reuptake....
  
  .
- Phenylpiperidine derivative Opioids: Meperidine/Pethidine, Tramadol
  Tramadol
  Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...
  
  , Methadone
  Methadone
  Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
  
  , Fentanyl, Dextropropoxyphene
  Dextropropoxyphene
  Dextropropoxyphene, manufactured by Eli Lilly and Company, is an analgesic in the opioid category. It is intended to treat mild pain and has, in addition, anti-tussive and local anesthetic effects. It has been taken off the market in Europe and the US due to concerns of fatal overdoses and...
  
  , Propoxyphene.
- Others: Brompheniramine
  Brompheniramine
  Brompheniramine , commonly marketed as its salt brompheniramine maleate is an antihistamine drug of the propylamine class...
  
  , Chlorpheniramine, Cocaine
  Cocaine
  Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
  
  , Cyclobenzaprine
  Cyclobenzaprine
  Cyclobenzaprine is a muscle relaxant medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. It is the most well-studied drug for this application, and it also has been used off-label for fibromyalgia treatment.- Mechanism of action :The mechanism...
  
  , Dextromethorphan
  Dextromethorphan
  Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...
  
  (DXM), Ketamine
  Ketamine
  Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
  
  , MDPV
  MDPV
  Methylenedioxypyrovalerone is a psychoactive drug with stimulant properties which acts as a norepinephrine-dopamine reuptake inhibitor . Reportedly, it has been sold since around 2004 as a designer drug. It is also known as MDPK, MTV, Magic, Maddie, Black Rob, Super Coke and PV...
  
  , 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...
  
  , Phencyclidine
  Phencyclidine
  Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
  
  (PCP), Pheniramine
  Pheniramine
  Pheniramine is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It has relatively strong sedative effects, and may sometimes be used off-label as an over-the-counter sleeping pill in a similar manner to other sedating antihistamines...
  
  , Sibutramine
  Sibutramine
  Sibutramine is an oral anorexiant. Until 2010 it was marketed and prescribed as an adjunct in the treatment of exogenous obesity along with diet and exercise...
  
  , Trazodone
  Trazodone
  Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...
  
  .
Serotonin, Norepinephrine, and/or Dopamine Releasers: 4-Methylaminorex (4-MAR), 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,...

, Benzphetamine
Benzphetamine
Benzphetamine is an anorectic drug marketed under this brand in the USA by Pharmacia. Benzphetamine is used as a short term adjunct in management of exogenous obesity. It is closely related to amphetamine.- Pharmacology :...

, Cathine
Cathine
Cathine, also known as d-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant...

, Cathinone
Cathinone
Cathinone, or Benzoylethanamine, is a monoamine alkaloid found in the shrub Catha edulis and is chemically similar to ephedrine, cathine and other amphetamines. Cathinone induces the release of dopamine from striatal preparations that are prelabelled either with dopamine or its precursors. It is...

, Diethylcathinone
Diethylcathinone
Amfepramone , is a stimulant drug of the phenethylamine, amphetamine, and cathinone chemical classes that is used as an appetite suppressant.- Pharmacology :Amfepramone itself lacks any affinity for the...

, Ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....

, Levmetamfetamine
Levmetamfetamine
Levomethamphetamine , is the levorotary of methamphetamine...

, Lisdexamfetamine, MDMA ("Ecstasy"), Methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, Pemoline
Pemoline
Pemoline was first synthesized in 1913 but it's activity was not discovered until the 1930s. Under the names it was used as a medication used to treat attention-deficit hyperactivity disorder and narcolepsy. Under the Convention on Psychotropic Substances, it is a Schedule IV drug...

, Phendimetrazine
Phendimetrazine
Phendimetrazine is a stimulant drug of the morpholine chemical class used as an appetite suppressant....

, Phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...

(PEA), Phentermine
Phentermine
Phentermine, a contraction of "phenyl-tertiary-butylamine", is a psychostimulant drug of the phenethylamine class, chemically related to amphetamine. It is used medically as an appetite suppressant....

, Propylhexedrine
Propylhexedrine
Propylhexedrine is a stimulant drug related to methamphetamine. It is used mainly to provide temporary symptomatic relief of nasal congestion due to colds, allergies and allergic rhinitis...

, Pseudoephedrine
Pseudoephedrine
Pseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It is used as a nasal/sinus decongestant and stimulant, or as a wakefulness-promoting agent....

, Phenylephrine
Phenylephrine
Phenylephrine is a selective α1-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure...

, Tyramine
Tyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...

.
Serotonin, Norepinephrine, and/or Dopamine Supplemental Precursors: 5-HTP, L-DOPA, L-Phenylalanine, L-Tryptophan, L-Tyrosine.
Local
Local anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...

and General anesthetic in surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

and dentistry
Dentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...

particularly those containing Epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

. There is no universally taught or accepted practice regarding dentistry and use of MAOIs such as Phenelzine and it is therefore vital to inform all clinicians especially dentists of the potential effect of MOAIs and Local Anesthesia. In preparation for dental work withdrawal from Phenelzine is specifically advised, however since this takes two weeks it is not always a desirable or practical option. Dentists using Local Anesthesia are advised to use a non-epinephrine anestetic such as Carbocaine at a level of 3%. Specific attention should be paid to blood pressure during the procedure and the level of the anestetic should be regularly and appropriately topped up since non-epinephrine anestetics take longer to come into effect and wear off faster. Patients taking Phenelzine are advised to notify their Psychiatrist prior to any dental treatment.
Certain Other Supplements: Hypericum perforatum ("St John's Wort"), Inositol
Inositol
Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol...

, Rhodiola rosea
Rhodiola rosea
Rhodiola rosea is a plant in the Crassulaceae family that grows in cold regions of the world. These include much of the Arctic, the mountains of Central Asia, the Rocky Mountains, and mountainous parts of Europe, such as the Alps, Pyrenees, Carpathian Mountains, Scandinavia, Iceland, Great...

, S-Adenosyl-L-Methionine (SAMe), L-Theanine.
Other Monoamine Oxidase Inhibitors.

It is recommended by the FDA to contact a physician or pharmacist before taking any drug while on an MAOI.

List of MAOIs

Various tryptamine

Tryptamine

Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...

and phenethylamine

Substituted phenethylamine

The substituted phenethylamines are chemical compounds with the 2-phenethylamine chemical structure modified at the phenyl ring, sidechain, and/or amino group. Some of them are psychoactive drugs, including stimulants, psychedelics, opioids, and entactogens, which exert their effects primarily...

/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...

derivatives such as αET

Alpha-Ethyltryptamine

α-ethyltryptamine , also known as etryptamine, is a psychedelic, stimulant and entactogen of the tryptamine chemical class.- History :...

, αMT, 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,...

(itself), methamphetamine

Methamphetamine

Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

, MDMA

Methylenedioxymethamphetamine

MDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...

, 4-MTA, PMA, 2C-T-7

2C-T-7

2C-T-7 is a psychedelic phenethylamine of the 2C family. In his book PiHKAL: A Chemical Love Story, Alexander Shulgin lists the dosage range as 10 to 30 mg. 2C-T-7 is generally taken orally, and produces psychedelic and entactogenic effects that last 8 to 15 hours...

, and 2C-T-21

2C-T-21

2C-T-21 is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. It was the first psychedelic drug known to contain six different chemical elements in the structure.-Chemistry:...

may also have weak to strong MAOI effects at high doses. Many other unlisted hydrazines like hydrazine

Hydrazine

Hydrazine is an inorganic compound with the formula N2H4. It is a colourless flammable liquid with an ammonia-like odor. Hydrazine is highly toxic and dangerously unstable unless handled in solution. Approximately 260,000 tons are manufactured annually...

(itself), monomethylhydrazine

Monomethylhydrazine

Monomethylhydrazine is a volatile hydrazine chemical with the chemical formula CH3 NH2. It is used as a rocket propellant in bipropellant rocket engines because it is hypergolic with various oxidizers such as nitrogen tetroxide and nitric acid...

, and phenylhydrazine

Phenylhydrazine

Phenylhydrazine is the chemical compound with the formula C6H5NHNH2. Organic chemists abbreviate the compound as PhNHNH2.- Chemical properties :...

have some MAOI properties as well.

Cultural references

In the episode "The Late Shift" of the TV detective drama Castle
Castle (TV series)
Castle is an American comedy-drama television series, which premiered on ABC on March 9, 2009. The series is produced by Beacon Pictures and ABC Studios. On January 10, 2011, Castle was renewed for a fourth season...

, Bobby Mann was taking an MAO inhibitor. His killer used this fact to trigger a negative interaction with the drug, leading Bobby's death through what seemed to be a normal heart attack.

In the episode "Cut" of Law & Order
Law & Order
Law & Order is an American police procedural and legal drama television series, created by Dick Wolf and part of the Law & Order franchise. It aired on NBC, and in syndication on various cable networks. Law & Order premiered on September 13, 1990, and completed its 20th and final season on May 24,...

, a surgeon prescribes painkillers that interact with an MAOI a patient was taking, leading to her death.

The pilot episode of Law and Order was similar to an actual event. Journalist Sidney Zion questioned the sudden death of his daughter Libby Zion at an ER room in Manhattan on Oct 4 1984. The cause of death was attributed to "mysterious infection". The father convinced authorities to launch a criminal investigation when it was discovered that several medications, including Demerol, were administered to his daughter, reacting with her Nardil medications. The DA sought charges of murder against a doctor, which approved use of restraints and narcotics when Libby became increasingly agitated. The case prompted many reforms in graduate medical education and limiting number of hours staff can work. Drug abuse was successfully argued as a major factor leading to her death.

Indications

Mode of action

Reversibility

Selectivity

Dangers

Withdrawal

Interactions

List of MAOIs

Cultural references

See also