Effects of antidepressants and other psychotropic drugs on melatonin release and pineal gland function.
Antidepressants and some other psychotropic drugs affect the synthesis and release of melatonin through several mechanisms. Monoamine oxidase (MAO)-inhibiting antidepressants increase pineal concentrations of the melatonin precursors, serotonin (5-HT) and N-acetyl serotonin (NAS), in rodents, and also increase pineal N-acetyl transferase activity as well as both daytime and nighttime plasma melatonin concentrations; they also elevate melatonin, 5-HT and NAS in the cerebrospinal fluid of non-human primates. In humans treated with the MAO-A selective inhibitor, clorgyline, or the nonselective inhibitor, tranylcypromine, increased plasma melatonin also occurs; in contrast, the MAO-B selective inhibitor, 1-deprenyl, does not affect plasma melatonin. Chronically-administered tricyclic antidepressants with prominent effects on monoamine uptake and on beta-adrenoceptors reduce pineal and plasma melatonin in rodents; however, in two studies in depressed patients, either no change or a significant elevation in nocturnal plasma melatonin followed 3 to 4 weeks treatment with desipramine. As depressed patients in these and several other recent studies had lower pretreatment nighttime melatonin peaks than controls, these findings may be relevant to the presynaptic and receptor adaptational consequences of chronic antidepressant drug treatment. The significant effects on melatonin of other drugs which affect monoamine function and have psychotropic effects, including lithium, propranolol, amphetamine and several monoamine precursors, together with recent observations of the existence of muscarinic and benzodiazepine receptors in the pineal gland are in accord with previous suggestions that the study of pineal function and melatonin production provides a valuable model system for psychopharmacological investigations.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D002940:Circadian Rhythm; D003010:Clorgyline / Q000494:pharmacology; D008550:Melatonin / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008954:Models, Biological; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011323:Primates; D011619:Psychotropic Drugs / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D008996:Monoamine Oxidase Inhibitors; D011619:Psychotropic Drugs; D008550:Melatonin; D003010:Clorgyline