Monoamine Oxidase Inhibitors and Their Role in Depression

The role of the monoamines, serotonin in mental illnesses including depression is well recognized. All antidepressant drugs in clinical use increase acutely the availability of these monoamines at the synapse either by inhibiting their neuronal reuptake, inhibiting their intraneuronal metabolism, or increasing their release by blocking the α2 autoand heteroreceptors on the monoaminergic neuron. This acute increase in the amount of the monoamines at the synapse has been found to induce long-term adaptive changes in the monoamine systems that end up in the desensitization of the inhibitory autoand heteroreceptors including the presynaptic α2 and 5-HT1B receptors and the somatodendritic 5-HT1A receptors located in certain brain regions. The desensitization of these inhibitory receptors would result in higher central monoaminergic activity that coincides with the appearance of the therapeutic response. Two types of MAO, i.e. type A (MAO-A) and type B (MAO-B).MAO-A oxidizes noradrenaline and serotonin; and MAO-B, mainly βphenylethylamine. In the human brain, MAO-A exists in catecholaminergic neurons, but MAO-B is found in serotonergic neurons and glial cells. MAO-A and MAO-B may be closely related to various neuropsychiatric disorders such as depression and Parkinson’s disease, and inhibitors of them are the subject of drug development for such diseases.