Antidepressive and antihypertensive effects of MAO-A inhibition: role of N-acetylserotonin. A review.
Acute administration of irreversible and reversible selective MAO-A inhibitors and high doses (or chronic administration of low doses) of relatively selective MAO-B inhibitors (but not of highly selective MAO-B inhibitors) suppressed MAO-A activity and stimulated N-acetylation of pineal serotonin into N-acetylserotonin, the immediate precursor of melatonin. Consequent increase of melatonin occurs only in > 21-days-old rats. The effect is strain (spontaneously hypertensive rats > Fisher344N > Wistar Kyoto > Sprague-Dawley) and gender (male > female) dependent. N-acetylserotonin increase after clorgyline was weaker in the light-primed aged (or young animals with lesioned suprachiasmatic nuclei) than in young intact or sham-operated rats. N-acetylserotonin increase after MAO-A inhibitors might mediate their antidepressive (N-acetylserotonin and melatonin exerted antidepressant-like activity in the mouse tail-suspension and frog tests) and antihypertensive effects (N-acetylserotonin, but not melatonin, decreased blood pressure in spontaneously hypertensive rats).
Oxenkrug
G F
GF
Department of Psychiatry, St. Elizabeth's Medical Center/Tufts University, Boston, MA 02135, USA.
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000378:metabolism / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
D000928:Antidepressive Agents; D000959:Antihypertensive Agents; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D008995:Monoamine Oxidase; C006389:N-acetylserotonin