Basic and clinical aspects of the activity of the new monoamine oxidase inhibitors.

The clinical relevance of the neurobiochemical and pharmacological properties of the new generation of monoamine oxidase inhibitors (MAOIs) is reviewed and discussed. The most distinctive characteristics of these drugs are the selectivity, competitive nature and reversibility of their MAO-inhibiting action. The most selective MAO-A inhibitors are moclobemide and brofaromine, with ratios between their MAO-A and MAO-B inhibiting potency (estimated in in vitro assays) of 1: greater than or equal to 1000 and 1:500, respectively, whereas the least selective drug is cimoxatone with a ratio of 1:66. If in vitro findings are considered, the most potent MAO-A inhibitor seems to be cimoxatone and the least potent toloxatone. After oral administration, however, cimoxatone, brofaromine and moclobemide appear to be about equally effective in inhibiting brain MAO-A. All these drugs are short acting and their MAO-inhibiting action is reversible within 24 h or, in the case of brofaromine, 48 h. Due to the selectivity and reversibility of the MAO-A inhibition, they were found to be less likely to induce large increases in the pressor responses to tyramine, both in animals and in man. In patients treated with 150 mg/day for 4 weeks, brofaromine, which appears to be the best-characterized drug in this respect, produced about a 4-fold increase in sensitivity to tyramine. Although the clinical antidepressant efficacy of these drugs remains to be confirmed in more extensive studies, based on their neurobiochemical and pharmacological properties, clear advantages in respect to their side-effect profiles are to be expected in comparison with the classical MAOIs.