In studies exploring the net physiological consequences of antidepressant drug treatment, the selective monoamine oxidase (MAO) type A inhibitor clorgyline and the non-selective inhibitor tranylcypromine were both found to increase early morning plasma melatonin concentrations in depressed patients, while the clinically less effective inhibitor of MAO-B, deprenyl, did not affect melatonin. In related animal studies, clorgyline had marked effects in reducing the firing rates of neurons in the locus coeruleus of rodents after both single, high dose clorgyline administration as well as after chronic treatment. Like other effects of clorgyline on Beta-adrenoceptors and cyclic AMP changes, this drug altered dopamine function (as reflected in apomorphine-induced stereotypy) only after chronic administration. In rhesus monkeys, a number of newer reversible MAO-A inhibitors had lesser effects on neuroamines and amine receptor functions than had been found with clorgyline and other clinically effective MAO-inhibitors, raising questions about their future utility as antidepressant agents, despite their more favorable side effect profile.
