Effects of antihistaminic drugs on feline brain monoamine metabolism

Abstract

Diphenhydramine and phenindamine were administered in various doses to cats and the time course of changes in monoamine metabolite levels in cerebrospinal fluid was determined. Diphenhydramine at a sedative dose did not alter 5-hydroxytryptamine or dopamine metabolism. Excitant doses of diphenhydramine elevated 5-hydroxyindolacetic acid levels, while homovanillic acid levels remained unchanged. At a convulsant dose, diphenhydramine lowered rectal temperature while elevating both 5-hydroxyindolacetic acid and homovanillic acid levels. Phenindamine, which reportedly produces only central nervous system (CNS) excitation and convulsions, caused excitation, tremor and stereotypy, while elevating 5-hydroxyindolacetic acid and homovanillic acid levels in cerebrospinal fluid. These data suggest that antihistaminic-induced sedation is not due to an alteration in brain 5-hydroxytryptamine or dopamine metabolism and that only 5-hydroxytryptamine metabolism is increased during CNS excitation. Stereotypic behavior after phenindamine may occur through a dopaminergic system as reflected by elevated levels of homovanillic acid in cerebrospinal fluid.