Biochemistry and pharmacology of moclobemide, a prototype RIMA View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1992-02

AUTHORS

W. Haefely, W. P. Burkard, A. M. Cesura, R. Kettler, H. P. Lorez, J. R. Martin, J. G. Richards, R. Scherschlicht, M. Da Prada

ABSTRACT

RIMA is a term for reversible inhibitors of monoamine oxidase (MAO) with preference for MAO-A; moclobemide is a prototype of this new class of antidepressants and is a highly selective inhibitor of MAO-A in vitro. This inhibition is reversible by dialysis in vitro, which accounts for the dose-dependent duration of in vivo enzyme inhibition of 12–24 h. Moclobemide increases the content of serotonin, noradrenaline and dopamine in the brain, and decreases that of their deaminated metabolites. Its biochemical, neurological and behavioural effects indicate that it increases the extracellular concentration of the classic monoamine neurotransmitters/neuromodulators — in particular 5-HT. Potentiation of the cardiovascular effects of tyramine is less pronounced after taking moclobemide than after irreversible MAO-A inhibitors. Understanding of the physiological role of MAO and of the events that link inhibition of the enzyme with modulation of neuronal activities in the CNS remains incomplete. A major physiological role of intraneuronal MAO is to keep cytosolic amine concentration very low, to enable the neuronal monoamine carriers to produce a net inward transport of monoamines, and thereby to act as the first step in the termination of action of extracellular monoamines. MAO is likely to have a similar function in non-monoaminergic cells with respect to the monoamine carriers they contain. In addition to the classic monoamines, “trace” amines may become functionally active after MAO inhibition. An alternative role for MAO is that of a scavenger, preventing natural substrates from accumulating in monoaminergic neurons and interacting with storage, release, uptake and receptor function of monoamines. More... »

PAGES

s6-s14

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf02246225

DOI

http://dx.doi.org/10.1007/bf02246225

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026661480

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/1546143


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