Similarity between tyramine-induced neurotoxicity and the coma of Reye's syndrome

BA Faraj, DB Caplan, EJ Malveaux, VM Camp and FM Ali

The objective of the present investigation was to determine whether or not tyramine induces coma in experimental animals with impaired mitochondrial monoamine oxidase function, and whether the coma in these animals was a function of increased cerebrospinal fluid (CSF) pressure. Ten mongrel dogs were treated (orally) daily with the monoamine oxidase- inhibiting drug, phenelzine (4.5 mg/kg), over a period of 1 month. The present studies indicated that in phenelzine-treated animals with liver disease and behavioral side effects (n = 4), the i.v. administration of tyramine (1 mg/kg) caused substantial elevation in CSF pressure that exceeded 30 mm Hg (initial pressure 12.5 +/- 2.1). This was followed by substantial accumulation of tyramine, dopamine and norepinephrine concentrations in CSF of these animals. The animals became comatose soon afterward. The administration of tyramine to pretreated (n = 10) or phenelzine-treated animals without liver disease (n = 6) caused only the expected transient increase in blood pressure but with no significant effect on CSF pressure of these animals. These animals recovered fully from the experiment without any ill effect. These studies suggest that tyramine may have obvious implications in the development of intracranial hypertension in Reye's syndrome.

Volume 226, Issue 2, pp. 608-615, 08/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics