EVIDENCE FOR RELEASE OF BRAIN AMINES BY RESERPINE IN PRESENCE OF MONOAMINE OXIDASE INHIBITORS: IMPLICATION OF MONOAMINE OXIDASE IN NOREPINEPHRINE METABOLISM IN BRAIN

¹ National Heart Institute, National Institutes of Health, Bethesda, Maryland

Evidence is presented that serotonin (5HT) and norepinephrine (NE) are released by reserpine from their brain storage depots in rabbits pretreated with monoamine oxidase inhibitors. Since MAO is inactivated, the free amine levels do not decline rapidly. The slow disappearance of the amines from brain may be attributable to the difficulty of their passage across the blood-brain barrier. It is concluded, therefore, that MAO is the enzyme chiefly responsible for the metabolism of NE as well as 5HT in brain. The evidence that MAO inhibitors do not prevent release of the amines by reserpine is based on three observations: (1) MAO inhibitors do not prevent the release of 5HT from rabbit platelets in vivo or in vitro; (2) temporary blockade with harmaline, a short acting competitive MAO inhibitor, does not block the release of brain amines by reserpine; (3) a variety of MAO inhibitors of various structures reverses the pharmacological action of reserpine and prevents the decline in amine levels.

Additional evidence that MAO is the principal enzyme in the inactivation of brain NE is the finding that pyrogallol, a catechol O-methyl-transferase (COMT) inhibitor, does not block the metabolism of brain arnines released by reserpine or counteract the sedative action of the alkaloid.

The postulate is advanced that MAO and COMT have different physiological roles; MAO is responsible for metabolism of NE and 5HT in tissues, where it may regulate the level of stored amines; COMT is responsible for inactivation of catecholamines after their release into the circulation.