Molecular Structure–Activity Relationships of Hydrazides Inhibiting Glutamic Acid Decarboxylase, GABA-α-Oxoglutarate Aminotransferase, and Monoamine Oxidase Activities in Chick Brain

Abstract

Several aryl and heteroaryl hydrazides were synthesized and evaluated for their inhibitory effects on glutamic acid decarboxylase (GAD), GABA-α-oxoglutarate aminotransferase (GABA-T), and monoamine oxidase (MAO) enzyme systems in chick brain 24 h after their intramuscular administration (0.75 mmol/kg). All compounds produced a reduction in GAD, GABA-T, and MAO activity. Structure–activity relationships indicated that the ring structure had a greater influence on the degree of GAD and GABA-T inhibition than did the N′-terminal group. In contrast, structural requirements for MAO inhibition were much more restrictive. The intramuscular administration of benzoic acid hydrazide to chicks 24 h prior to their being exposed to oxygen at high pressure provided significant protection against the onset of the hyperbaric oxygen-induced seizures.