The role of monoamine oxidase and catechol O-methyltransferase in dopaminergic neurotransmission.
The action of dopamine (DA) released in the synaptic cleft is mainly terminated by its reuptake and catabolism by the enzymes monoamine oxidase (MAO) and catechol O-methyltransferase (COMT). Preclinical data show that the reduction of the catabolism of DA elicited by MAO and COMT inhibitors leads to an enhancement of DA neurotransmission. Moreover, there is evidence suggesting that MAO-B inhibition might protect DA neurons from oxidative stress. Nevertheless, due to differences in enzyme localization and activity between man and rodents, results obtained in experimental animals might not reflect the actual situation in humans. Today the availability of potent and selective MAO and COMT inhibitors makes it feasible for the clinician to test whether the blockade of catabolic enzymes would result in a symptomatic improvement in Parkinsonian patients, and whether MAO-B inhibition might additionally exert a neuroprotective effect.
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Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
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D002394:Catechol O-Methyltransferase / Q000502:physiology*; D065098:Catechol O-Methyltransferase Inhibitors; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008995:Monoamine Oxidase / Q000502:physiology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine