Moclobemide: Evolution, Pharmacodynamic, and Pharmacokinetic Properties

Abstract

The benzamide moclobemide is a reversible inhibitor of monoamine-oxidase-A (RIMA). It has been extensively evaluated in the treatment of a wide spectrum of depressive disorders and less extensively in anxiety disorders. While clinical aspects will be presented in a subsequent review, this article focuses primarily on moclobemide's evolution, pharmacodynamic and pharmacokinetic properties. In particular, the effects on neurotransmission and intracellular signal transduction, the neuroendocrine system, the tyramine pressure response and animal models of depression are surveyed. In addition, other CNS effects are reviewed with special respect to experimental serotonergic syndrome, anxiolytic and antinociceptive activity, sleep, cognition and driving performance, neuroprotection and seizures.

Death following acute poisoning by moclobemide

“…The concentration of several drugs in vitreous humor and in cerebrospinal fluid have previously been reported to be closely related to the unbound fraction in plasma. The CSF to whole blood ratio is 0.76, a value which is in the same range as the value of the bound fraction of moclobemide in plasma (Fb ¼ 0:5) [1,4]. A high concentration of moclobemide was detected in the bile.…”

“…In the human brain, about three-fourth of MAO belongs to the B type [1]. MAO-A is mainly localised in noradrenergic neurons in the locus coeruleus [1]. Recently, the effects of moclobemide on MAO-A inhibition have been studied with positron emission tomography.…”

“…As a consequence of MAO-A inhibition, moclobemide increased the levels of brain neurotransmitter amines and in parallel decreased their main deaminated metabolites. In depressed patients, therapeutic administration of moclobemide reduced blood concentrations of metabolites of amine neurotransmitters and induced long-term up-and down-regulation of adrenoreceptors [1].…”

“…The distribution of MAO activity varies with tissues. In the human brain, about three-fourth of MAO belongs to the B type [1]. MAO-A is mainly localised in noradrenergic neurons in the locus coeruleus [1].…”

“…1) is a short acting selective and reversible inhibitor of monoamine-oxidase A (MAO-A) used as an anti-depressant and for the treatment of social phobia [1]. In human brain, serotonin, norepinephrine and epinephrine are preferentially deaminated by MAO-A, whereas dopamine and 2-phenylethylamine are favoured substrates of MAO-B [1,2].…”