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 h as been vindicated in practice. Despite this, the pharmacological basi s for their actions is unclear. Studies with the irreversible inhibito r clorgyline have shown that chronic but not acute treatment of rats l eads to a significant enhancement of noradrenaline release from periph eral sympathetic nerves and cerebral cortex together with a more effec tive inhibition of MAO-A, as shown by reduction in levels of deaminate d metabolites in cortical microdialysis fluid. Reversible inhibitors, however, do not have a cumulative effect on MAO inhibition and may hav e different effects on noradrenaline release. Reversible inhibitors di d not produce the acute reduction in sympathetic nerve activity seen w ith clorgyline, which may be one factor in explaining their milder sid e effect profile. Other aspects of the pharmacology of reversible and irreversible selective inhibitors of MAO-A are reviewed.