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PubMed1977

The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo(b)furan-m-carboxamido)-ethyl)-benzenesulphonyl]-N'-cyclohexylurea (NOVO CS 476). I. Pharmacological studies on the hypoglycaemic effect.

The new sulphonylurea CS 476 has been shown to be a potent hypoglycaemic agent. In normal fasting dogs, rabbits, rats and mice the maximal hypoglycaemia produced by intravenous administration of CS 476 was comparable on a weight basis to that produced by glibenclamide. Randomized Latin square experiments in dogs showed that 0.03 mg/kg orally of CS 476 and of glibenclamide caused the same maximal decrease of blood glucose and that CS 476 had the shorter duration of action. CS 476 had no hypoglycaemic effect in totally pancreatectomized dogs nor in streptozotocin diabetic dogs and rats. The insulin releasing activity was studied in dogs after intravenous and oral administration of equipotent doses of CS 476, tolbutamide and glibenclamide. It was found that the insulin curves after CS 476 tended to have a plateau-like maximum like those after glibenclamide although the duration of effect was shorter.

Administration, Oral↗
PubMed1977

The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo(b)furan-7-carboxamid o)-ethyl)-benzenesulphonyl]-N'-cyclohexlurea (NOVO CS 476). III. General pharmacological studies.

The new sulphonylurea CS 476 was tested for positive iontropic effect on the isolated cat papillary muscle. Unlike tolbutamide CS 476 had no positive inotropic effect. CS 476 had no adverse effect on blood pressure in dogs, cats and rats nor on the electrocardiogram of dogs in doses up to ten times the therapeutic dose. Unlike chlorpromide CS 476 did not potentiate the effect of exogenous antidiuretic hormone in hydrated dogs. In therapeutic concentrations the drug had no effect on smooth muscle preparations. 1,000-10,000 times therapeutic concentrations had a papaverine-like effect - similar to therapeutic concentrations of tolbutamide.

Animals↗