CONVULSANT ACTION OF HYDRAZIDES AND REGIONAL CHANGES IN CEREBRAL GAMMA-AMINOBUTYRIC ACID AND PYRIDOXAL-PHOSPHATE CONCENTRATIONS

Abstract— Regional changes in the concentration of GABA and pyridoxal phosphate were determined in rat brain after i.p. administration of convulsant doses of methyldithiocarbazinate (11 mg/kg), isonicotinic acid hydrazide (250 mg/kg) and thiosemicarbazide (25 mg/kg). At 15 and 30 min after methyldithiocarbazinate GABA concentrations were reduced in all brain regions (except ventral mid‐brain). After 30 min the largest decrease was in the cerebellum (41%) and the smallest decrease in the hypothalamus (20%). Pyridoxal phosphate concentrations were decreased by 39‐57%. After isonicotinic acid hydrazide. the regional decreases in GABA concentration were smaller and of slower onset than those seen after methyldithiocarbazinate. The pons‐medulla was the first region to show a decrease (at 15 min) whereas a decrease was not seen in the frontal cortex until 45 min. Regional decreases in pyridoxal phosphate were smaller than those seen after methyldithiocarbazinate. After thiosemicarbazide, small regional decreases in GABA concentration were observed only in the hypothalamus, cerebellum, pons‐medulla and posterior cortex (13‐18%) and there was no apparent correlation between regional decreases in pyridoxal phosphate and regional decreases in GABA. Copyright © 1979, Wiley Blackwell. All rights reserved