The rat studies presented in this manuscript show that the new non-hydrazine compounds moclobemide, brofaromine and toloxatone have a profile typical of monoamine oxidase-A (MAO-A) inhibitors. These inhibitors are short-acting (16-24 h), reversible, non-hepatotoxic and have only low liability to potentiate tyramine pressor effects (cheese-effect). The present results in rats and the clinical trials provide evidence that moclobemide is an orally active MAO-A inhibitor which, due to its remarkably low tyramine potentiating pressor effects and to its lack of anticholinergic activity, has a very attractive pharmacological profile. In contrast to moclobemide, tranylcypromine is an irreversible and mixed MAO-A and MAO-B inhibitor with long-lasting effects. This hydrazine derivative is not devoid of hepatotoxic effects and markedly potentiates tyramine pressor effects. Moclobemide, being a particularly safe MAO-A inhibitor, seems to be an effective new compound for the therapy of exogenous and endogenous depressive states.