الفهرس 
Oral antidiabetic agentsOnly 14 pages are availabe for public view
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Abstract
The o r a l a n t i d i a b e t i c agents, tolbutamide (Rastinon) , glycodi a z ine (Lycanol ) and glibenclamide (~aonil,) pos s e s s some diverse pharmacological a c t i o n s a p a r t from t h e i r hypoglycemic e f f e c t . 1. Glycodiazine and tolbutamide have i n h i b i t o r y e f f e c t s on t h e r a t u t e r u s , guinea-pig ileum and r a b b i t i n t e s t i n e , which is not due t o syinpathomimetic-like a c t i v i t y , they have \. no e f f e c t on t h e i n h i b i t o r y response caused by syipathetic nerve stimulation of t h e r a b b i t i n t e s t i n e nor t o axogenously added n o r a d r e n a l i n e Glibenc1ami.de caused s l i g h t p o t o n t i a t i o n of sTflnpathetic nerve stiinulation but not t o exogenou-sly added noradrenaline . 2. Tolbutamide, glycodiazine and glibenclad.de have no effect on t h e neuromuscular junction. 3. Glycodiazine and ~libenclarnide increased t h e histarnine content o f t h e p y l o r i c and fundic regions of the r a t stoiaach. This increase may be t h e rzsult of i n c r e a s e i n t h e a c t i v i t y of the enzyine histidine diicarboxylase and/or an incraase i n t h e degree of binding of histamine i n thz stomach. This i n c - rease i n histamine content i s probably not due t o hypoglycemia as tolbutamide did not a f f e c t t h e histarnine content of t h e stomach or t h e i n t e s t i n e . Glibenclamide increased t h e histamine content of the i n t e s t i n e which may be due t o a decrease i n t h e l e v e l of ths enzyme histaminase. 4. Tolbutamide, glycodiazine and glibenclamide have antiinflammatory a c t i v i t y revealed by reduction of granuloma weight caused by cotton p e l l e t implantation which may be due t o increased steroidogenesis- 5. No oestrogenic a c t i v i t y was found f o r tolbutamide, glycodiazine or glibenclamide. A mild antiandrogenic acti7Jity was found f o r glibenclamide and glycodiazine and none f o r tolbutamide. 6. Glycodiazine and glibencla~nide caused an increase in the histamine content of the p r o s t a t e gland. Tolbutamide f a i l e d t o increase but a c t u a l l y decreased t h e histamine content of t h e . p r o s t a t e gland. 7. Injected intravenously tolbutamide and glibenclamide caused a r i s e i n cat and r a b b i t blood pressure. The r i s e i n blood pressure was not blocked by phenoxybenzamine. Glycodiazine caused a r i s e i n blood pressure and tachyphylaxis occurred on repeated administration. Tolbutarnide, glycodiazine and glibenclamide caused p o t e n t i a t i o n of t h e r i s e i n cat blood pressure caused by i n j e c t i o n o f a d r e n a l i n e , noradrenaline and angiotensin. The responsesof t h e rabbit blood pressure t o noradrenaline and angiotensin were not affected by tolbutamide and glycodiazine . Tolbutamide and glibenclamide potentiated t h e r e f l e x r i s e i n blood pressure caused by occlusion of both carotid a r t e r i e s but glycodiazine had no e f f e c t . 8. Tolbutamide, glycodiazine and glibenclamide increased the sleeping t i n e of hexobarbital sodium. This may be due t o i n h i b i t i o n of t h e l i v e r micro soma1 enzymes responsible f o r metabolism of b a r b i t u r a t e s . However, tolbutamide may have a biphasic e f f e c t causing f i r s t i n h i b i t i o n of the microsomal enzyme a c t i v i t y followed by an a c t i v a t i o n.