Reversible and selective inhibitors of monoamine oxidase A in mental and other disorders

Abstract

The clinically tested reversiblc inhibitors of monoamine oxidase A (RIMAs) include brofaromine, moclobemide and toloxatone. Moclobemide has shown unequivocal antidepressant activity against serious deprcssivc illness in 4 placebo‐controlled double‐blind trials. It has been compared with amitriptyline, imipramine, clomipramine, desipramine, maprotiline, fluoxetine, fluvoxamine, tranylcypromine. toloxatone, mianserin and amineptine in the treatment of depressive disorders. Meta‐analysis showed convincing evidence of moclobemide efficacy, comparable with the most potent antidepressants available. The efficacy of moclobemide has been demonstrated in psychotic and non‐psychotic depression, in depression with and without melancholia, in endogenous depression (both unipolar and bipolar), in retarded depression and in agitated depression. The efficacy of moelobemide, allied to the unusually benign side effect profile, has led to exploration of its use in other disorders. Two small studies have given encouraging results in the treatment of attention‐deficit hyperactivity disorder. Large placebo‐controlled studies have shown the activity of moclobemide in the depression that accompanies dementia (such as senile dementia of Alzheimer type). The results also suggested that, in this patient population, cognitive ability improved in parallel. Social phobia has also been shown to improve on treatment with either moclobemide or brofaromine. Clinical trials are in progress on the effect of moclobemide in chronic fatigue syndrome. Moreover, there are encouraging results with the use of brofaromine and moclobemide in panic disorder. Other disorders in which treatment with RIMA is of interest include agoraphobia, bulimia, borderline personality disorder, post‐traumatic stress disorder, compulsive hair pulling (trichotillomania), dysmorphophobia, kleptomania as well as various anxiety syndromes.

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

“…Future work on MAO inhibitors was driven by two aspects: first, the search for safer, reversible inhibitors of MAO and, second, differentiation of MAO-A, which mainly metabolizes 5-HT and NA, from MAO-B which preferentially metabolizes DA and phenethylamines like tyramine (Lotufo-Neto et al, 1999;Priest et al, 1995). This work resulted in the launch of the reversible and well-tolerated MAO-A inhibitor moclobemide in the EU for the treatment of depression and social anxiety (Kriston et al, 2014;Lotufo-Neto et al, 1999).…”

Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

“…The reversible inhibitors of monoamine oxydase, brofaromine and moclobemide were recently introduced into therapy to minimize the risk of serious adverse reactions associated with the irreversible MAOIs. Clinical trials have shown these drugs to be effective antipanic agents [20,83,99,101]. SSRIs are active in reducing panic symptomatology and are better tolerated than BZs, tricyclic antidepressants and MAOIs.…”

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

“…buspirone and tandospirone) (Barradell and Fitton, 1996;Fulton and Brogden, 1997). In addition, only selective 5-HT re-uptake and monoamine-oxidase inhibitors have been successfully used in the chronic treatment of panic attacks, obsessive -compulsive, and posttraumatic stress disorders (Billett et al, 1997;Buller, 1995;Fichtner et al, 1997;Liebowitz et al, 1990;Priest et al, 1995;Westenberg, 1996). Although interest in this research area has steadily decreased, novel 5-HT-modulating agents are still being developed.…”