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.
Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.
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.
A biogenic amine is a biogenic substance with one or more amine groups. They are basic nitrogenous compounds formed mainly by decarboxylation of amino acids or by amination and transamination of aldehydes and ketones. Biogenic amines are organic bases with low molecular weight and are synthesized by microbial, vegetable and animal metabolisms. In food and beverages they are formed by the enzymes of raw material or are generated by microbial decarboxylation of amino acids.
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).
Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi-subunit enzyme in most prokaryotes and in the chloroplasts of most plants and algae, whereas it is a large, multi-domain enzyme in the cytoplasm of most eukaryotes. The most important function of ACC is to provide the malonyl-CoA substrate for the biosynthesis of fatty acids. The activity of ACC can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. The human genome contains the genes for two different ACCs—ACACA and ACACB.
Clorgiline (INN), or clorgyline (BAN), is a monoamine oxidase inhibitor (MAOI) structurally related to pargyline which is described as an antidepressant. Specifically, it is an irreversible and selective inhibitor of monoamine oxidase A (MAO-A). Clorgiline was never marketed, but it has found use in scientific research. It has been found to bind with high affinity to the σ1 receptor (Ki = 3.2 nM) and with very high affinity to the I2 imidazoline receptor (Ki = 40 pM).
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.
Amine oxidase (copper-containing) (AOC) (EC 1.4.3.21 and EC 1.4.3.22; formerly EC 1.4.3.6) is a family of amine oxidase enzymes which includes both primary-amine oxidase and diamine oxidase; these enzymes catalyze the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. They act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor:
Cystathionine beta-lyase, also commonly referred to as CBL or β-cystathionase, is an enzyme that primarily catalyzes the following α,β-elimination reaction
In enzymology, a cystathionine gamma-synthase is an enzyme that catalyzes the formation of cystathionine from cysteine and an activated derivative of homoserine, e.g.:
Amine oxidase, copper containing 3 (AOC3), also known as vascular adhesion protein (VAP-1) and HPAO is an enzyme that in humans is encoded by the AOC3 gene on chromosome 17. This protein is a member of the semicarbazide-sensitive amine oxidase family of enzymes and is associated with many vascular diseases.
Semicarbazide-cadmium therapy was an experimental cancer therapy that was tested in several clinical trials in the Soviet Union during the 1960s. Semicarbazide is an irreversible inhibitor of semicarbazide-sensitive amine oxidase (SSAO), an enzyme possibly involved in exacerbation of inflammation. Cadmium is a heavy metal and can also induce apoptosis.
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.
Methylamine dehydrogenase (amicyanin) (EC 1.4.9.1, amine dehydrogenase, primary-amine dehydrogenase) is an enzyme with systematic name methylamine:amicyanin oxidoreductase (deaminating). This enzyme catalyses the following chemical reaction:
Athel Cornish-Bowden is a British biochemist known for his numerous textbooks, particularly those on enzyme kinetics and his work on metabolic control analysis.
4-Hydroxyphenylacetaldehyde, also known as p-hydroxyphenylacetaldehyde, is a natural product with the formula HOC6H4CH2CHO. It is a derivative of phenylacetaldehyde and occurs as a white solid at room temperature.
