Moclobemide - History

History

Irreversible MAOI antidepressants were discovered accidentally in the 1950s but their popularity declined as their toxicity especially their dangerous food interactions became apparent and rival the tricyclic antidepressants were discovered. Reversible MAOIs were developed in the hope that they would exert efficacy in depressive disorders but with less of the toxicity of the older irreversible compounds; moclobemide's discovery and marketing brought the renewed interest in MAOIs due to an absence of dangerous tyramine food interactions and potent antidepressant effects. In 1992 moclobemide was launched onto the world markets. Moclobemide was the first reversible MAO-A inhibitor to be widely marketed; Moclobemide as well as other newer antidepressants such as the SSRIs lead to changes in prescribing patterns and broadened the treatment options for the management of depressive disorders.

The discovery of moclobemide in 1972 in Switzerland, as an antidepressant came about after it was initially investigated as a possible lipid lowering drug or antibiotic; when tests failed to demonstrate any antibiotic or antilipaemic properties; it was then tested for anti-cholinergic properties to see if it was a possible antidepressant but these tests also proved negative, leading researchers to think it may, in fact, be an antipsychotic; finally its reversible MAO-A properties as well as its lack of tyramine pressor effect. Clinical trials were commenced for moclobemide's effectiveness in the treatment of depression. It was first approved in the UK and Europe as the first reversible and selective inhibitor of MAO-A an is now approved in over 50 countries world wide. Subsequent research found that moclobemide is well tolerated in elderly patients and far superior to tricyclic antidepressants in terms of side effects/tolerability as well as being much safer in overdose; with regard to effectiveness in the treatment of depression, moclobemide was determined to be as effective as all major antidepressant drug classes. There is no need for dietary restrictions in contrast to people on irreversible MAOIs and apart from an important interaction with other serotonergic enhancing agents such as SSRIs and pethidine, there are few serious drug interactions; because of these benefits of moclobemide over existing antidepressant drugs, moclobemide became regarded as a beneficial addition to medical 'prescribing arsenal'. Additionally moclobemide was found to, unlike most other antidepressants on the market, to actually improve all aspects of sexual function. It is the only reversible MAOI in use in clinical practice. The fact that moclobemide's pharmacokinetic properties are unaltered by age, that cognition is improved in the elderly, and moclobemide has low potential for food and drug interactions opened up a new avenue for the treatment of major depressive disorder. Due to a lack of financial incentive, such as the costs of conducting the necessary trials to gain approval, moclobemide is unavailable in the USA pharmaceutical market.