Anti-ulcerogenic activity of GABA and GABA mimetic agents in rats

To elucidate the involvement of peripheral gamma- aminobutyric acid (GABA) and some GABA-mimetic agents in different models of gastric and duodenal ulcerations in rats and guinea pigs, effects of GABA, baclofen (GABAB agonist), diazepam, gamma-butyrolactone (GABA receptor agonist), sodium valproate, isoniazid (GABA-T inhibitor) and glycine (an inhibitory neurotransmitter), given po or ip were studied. All the drugs significantly reduced the ulcer index, incidence and number of ulcer in various models of gastric ulcers except glycine which failed to protect in reserpine-induced ulcers in rats. None of the drugs, except diazepam, had any protective effect on histamine-induced gastric ulcers in guinea pigs. Similarly, no protection was observed by any drug against cysteamine-induced duodenal ulcers in rats, while sodium valproate, isoniazid and glycine significantly decreased number of ulcers against histamine-induced duodenal ulcer in guinea pigs. The results suggest that GABA and GABA-mimetic agents, and glycine, an inhibitory neurotransmitter, afforded protection against some experimental models of peptic ulcer in rats. The effects appear to be due to their inhibitory effect on mucosal defensive factors.