Molecular structure--activity relationship of hydrazides inhibiting glutamic acid decarboxylase, GABA-alpha-oxoglutarate aminotransferase, and monoamine oxidase activities in chick brain.
Several aryl and heteroaryl hydrazides were synthesized and evaluated for their inhibitory effects on glutamic acid decarboxylase (GAD), GABA-alpha-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.
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology; D001565:Benzoates; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002645:Chickens; D005971:Glutamates; D006834:Hydrazines / Q000494:pharmacology*; D006931:Hyperbaric Oxygenation; D007656:Ketoglutaric Acids; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000637:Transaminases / Q000037:antagonists & inhibitors*; D005680:gamma-Aminobutyric Acid
D000927:Anticonvulsants; D001565:Benzoates; D005971:Glutamates; D006834:Hydrazines; D007656:Ketoglutaric Acids; D008996:Monoamine Oxidase Inhibitors; D005680:gamma-Aminobutyric Acid; D000637:Transaminases; D002262:Carboxy-Lyases