GABAERGIC EFFECT OF CERTAIN ORAL HYPOGLYCEMIC DRUGS IN NORMAL AND DIABETIC ADULT MALE ALBINO MICE

The effect of certain oral hypoglycaemic drugs, glibenclamide (0.5, 2. 5 and 5 mg kg(-1)), glipizide (1, 4 and 8 mg kg(-1)), gliclazide (10, 40 and 80 mg kg(-1)) and metformin (125, 375 and 750 mg kg(-1)) on the gamma-aminobutyric acid (GABA) content of different brain regions (ce rebral cortex, thalamus hypothalamus, midbrain and cerebellum, pens an d medulla) of adult male albino, normal and diabetic mice was investig ated after seven daily oral doses. Glibenclamide (0.5 mg kg(-1)) signi ficantly increased the GABA content in thalamus hypothalamus and midbr ain regions of normal mice, as well as in the thalamus hypothalamus of diabetic animals. At a dose of 2.5 mg kg(-1) it significantly increas ed the GABA content in different brain regions of normal mice, as well as in cerebral cortex, thalamus hypothalamus and midbrain regions of diabetic animals. However, a higher dose of glibenclamide (5 mg kg(-1) ) had no significant effect. Glipizide (1 mg kg(-1)), although without effect on GABA content of normal mice, significantly increased it in the thalamus hypothalamus of diabetic animals. At a dose of 4 mg kg(-1 ) it significantly increased the GABA content in cerebral cortex of no rmal mice, as well as in cerebral cortex, thalamus hypothalamus and mi dbrain of diabetic animals. On the other hand, a higher dose of glipiz ide (8 mg kg(-1)) significantly decreased the GABA content in midbrain and cerebellum, pens and medulla of normal mice, while there was no e ffect in diabetic animals. Gliclazide (10 mg kg(-1)) had no effect on the GABA content of normal animals, while a significant increase in ce rebral cortex and midbrain occurred in diabetic mice. At a dose of 40 mg kg(-1) it did not affect the GABA content either in normal or diabe tic mice. On the other hand, a dose of 80 mg kg(-1) produced a signifi cant decrease in GABA content in both cerebral cortex and cerebellum, pens and medulla regions of normal, as well as in the cerebral cortex and thalamus hypothalamus of diabetic mice. Although different doses o f metformin had no effect on normal brain GABA content, it induced a s ignificant increase in different brain regions of diabetic mice. As br ain GABA content has a highly significant correlation with excitabilit y, these changes may be of interest in relation to drug-drug interacti ons.