Pharmacology of reversible and selective inhibitors of monoamine oxidase type A

The concept of reversible type A monoamine oxidase (MAO-A) inhibitors as effective antidepressant drugs with a minimal side effect profile has been vindicated in practice. Despite this, the pharmacological basis for their actions is unclear. Studies with the irreversible inhibitor clorgyline have shown that chronic but not acute treatment of rats leads to a significant enhancement of noradrenaline release from peripheral sympathetic nerves and cerebral cortex together with a more effective inhibition of MAO-A, as shown by reduction in levels of deaminated metabolites in cortical microdialysis fluid. Reversible inhibitors, however, do not have a cumulative effect on MAO inhibition and may have different effects on noradrenaline release. Reversible inhibitors did not produce the acute reduction in sympathetic nerve activity seen with clorgyline, which may be one factor in explaining their milder side effect profile. Other aspects of the pharmacology of reversible and irreversible selective inhibitors of MAO-A are reviewed.