Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.
Monoamine oxidases (MAO) are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase. The MAOs belong to the protein family of flavin-containing amine oxidoreductases.
Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.
Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively.
Tyramine, also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs).
Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or tablet taken by mouth or orally disintegrating tablets taken on the tongue for Parkinson's disease and as a patch applied to skin for depression.
Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or "second-generation" TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities.
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism. Although they can be synthesized within parent monoamine neurotransmitter systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.
Pargyline (brand name Eutonyl) is an irreversible selective monoamine oxidase (MAO)-B inhibitor drug (IC50 for MAO-A is 0.01152 μmol/L and for MAO-B is 0.00820 μmol/L) It was brought to market in the US and the UK by Abbott in 1963 as an antihypertensive drug branded "Eutonyl". It was one of several MAO inhibitors introduced in the 1960s including nialamide, isocarboxazid, phenelzine, and tranylcypromine. By 2007 the drug was discontinued and as of 2014 there were no generic versions available in the US. In addition to its actions as an MAOI, pargyline has been found to bind with high affinity to the I2 imidazoline receptor (an allosteric site on the MAO enzyme).
Lobeline is a piperidine alkaloid found in a variety of plants, particularly those in the genus Lobelia, including Indian tobacco, Devil's tobacco, great lobelia, Lobelia chinensis, and Hippobroma longiflora. In its pure form, it is a white amorphous powder which is freely soluble in water.
N-Methylphenethylamine (NMPEA) is a naturally occurring trace amine neuromodulator in humans that is derived from the trace amine, phenethylamine (PEA). It has been detected in human urine and is produced by phenylethanolamine N-methyltransferase with phenethylamine as a substrate, which significantly increases PEA's effects. PEA breaks down into phenylacetaldehyde which is further broken down into phenylacetic acid by monoamine oxidase. When this is inhibited by monoamine oxidase inhibitors, it allows more of the PEA to be metabolized into nymphetamine (NMPEA) and not wasted on the weaker inactive metabolites.
Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene.
A reuptake inhibitor (RI) is a type of drug known as a reuptake modulator that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.
Bifemelane (INN) (Alnert, Celeport), or bifemelane hydrochloride (JAN), also known as 4-(O-benzylphenoxy)-N-methylbutylamine, is an antidepressant and cerebral activator that is widely used in the treatment of cerebral infarction patients with depressive symptoms in Japan, and in the treatment of senile dementia as well. It also appears to be useful in the treatment of glaucoma. Bifemelane acts as a monoamine oxidase inhibitor (MAOI) of both isoenzymes, with competitive (reversible) inhibition of MAO-A (Ki = 4.20 μM) (making it a reversible inhibitor of monoamine oxidase A (RIMA)) and non-competitive (irreversible) inhibition of MAO-B (Ki = 46.0 μM), and also acts (weakly) as a norepinephrine reuptake inhibitor. The drug has nootropic, neuroprotective, and antidepressant-like effects in animal models, and appears to enhance the cholinergic system in the brain.
A norepinephrine–dopamine reuptake inhibitor (NDRI) is a drug used for the treatment of clinical depression, attention deficit hyperactivity disorder (ADHD), narcolepsy, and the management of Parkinson's disease. The drug acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter (NET) and the dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of both norepinephrine and dopamine and, therefore, an increase in adrenergic and dopaminergic neurotransmission.
d-Deprenyl, also known as or dextro-N-propargyl-N-methylamphetamine, is an MAO-B inhibitor that metabolizes into d-amphetamine and d-methamphetamine and is therefore also a norepinephrine–dopamine releasing agent. It is the opposite enantiomer of l-deprenyl (selegiline).
Amiflamine (FLA-336) is a reversible inhibitor of monoamine oxidase A (MAO-A), thereby being a RIMA, and, to a lesser extent, semicarbazide-sensitive amine oxidase (SSAO), as well as a serotonin releasing agent (SRA). It is a derivative of the phenethylamine and amphetamine chemical classes. The (+)-enantiomer is the active stereoisomer.
Mofegiline (MDL-72,974) is a selective, irreversible inhibitor of monoamine oxidase B (MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) which was under investigation for the treatment of Parkinson's disease and Alzheimer's disease, but was never marketed.
Primary-amine oxidase, also known as semicarbazide-sensitive amine oxidase (SSAO), is an enzyme (EC 1.4.3.21) with the systematic name primary-amine:oxygen oxidoreductase (deaminating). This enzyme catalyses the following chemical reaction
Acetryptine (INN), also known as 5-acetyltryptamine (5-AT), is a drug described as an antihypertensive agent which was never marketed. Structurally, acetryptine is a substituted tryptamine, and is closely related to other substituted tryptamines like serotonin (5-hydroxytryptamine). It was developed in the early 1960s. The binding of acetryptine to serotonin receptors does not seem to have been well-investigated, although it was assessed at the 5-HT1A and 5-HT1D receptors and found to bind to them with high affinity. The drug may also act as a monoamine oxidase inhibitor (MAOI); specifically, as an inhibitor of MAO-A.
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