[Monoamine oxidase as a target for drug action].
Monoamine oxidase (MAO, EC 1.4.3.4), a flavine-containing enzyme catalyzing the oxidative deamination of monoamines, is located in the outer mitochondrial membrane and exhibited in virtually all tissues of mammals. As the family of MAO substrates includes both important neurotransmitters and hormones (i.e. serotonin, dopamine, adrenaline, noradrenaline) as well as biologically active dietary amines, such as tyramine (an indirectly acting sympathomimetic amine) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP a Parkinsonian producing exogenous neurotoxin), it is commonly accepted that MAO may play a critical role in the regulation of central nervous system activity and contribute to the pathogenesis of human neurodegenerative and depressive disorders. Fifty years ago the first generation of MAO inhibitors was developed and applied in therapy as anti-depressive compounds. However, for many years MAO inhibitors were considered useless in therapy due to the serious side effects induced by these drugs. Recently, MAO and its inhibitors are again in the center of scientific and pharmacological interest, providing new drugs for the therapy of Parkinson's disease, Alzheimer's disease, and various types of depression. Moreover, a beneficial pharmacological action of currently available MAO inhibitors, extending far beyond the MAO-B inhibitory properties, encourages investigators to search for new compounds exhibiting no side effects.This article gives a brief overview of the physiological importance of MAO and the biochemical and pharmacological potential of its inhibitors, with a consideration of their importance in the therapy of various disorders in humans.
Drozak
Jakub
J
Zakład Regulacji Metabolizmu, Instytut Biochemii, Wydział Biologii Uniwersytetu Warszawskiego. jdrozak@biol.uw.edu.pl
Kozłowski
Marcin
M
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy; D014439:Tyramine / Q000378:metabolism*
D000928:Antidepressive Agents; D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D014439:Tyramine