Special pharmacology of the new sulfonylurea glimepiride

Glimepiride (Hoe 490) is a new sulfonylurea. After oral administration of Hoe 490 to rabbits, blood glucose was lowered 3.5 times more than after glibenclamide (HB 419) and after intravenous administration, 2.5 times more. This superiority in efficacy was demonstrated by onset, maximum and duration of action. In rats, intravenous and oral Hoe 490 has a much shorter effect on blood glucose than HB 419, but the initial effect of Hoe 490 orally was up to 6 times and i.v. up to 2 times stronger than that of HB 419. In dogs, oral and intravenous Hoe 490 had a considerably longer blood glucose-lowering effect than HB 419. However, the effect of intravenous Hoe 490 was only half as intense as that of HB 419 in the first hours after treatment and the effect of oral Hoe 490 was initially stronger and thereafter temporarily distinctly weaker than that of HB 419. The more rapid decrease in blood glucose in the dog after oral administration of Hoe 490 was accompanied by a correspondingly earlier and higher plasma insulin increase. In accordance with the less intense initial blood glucose decrease in the dog after intravenous Hoe 490 there was a weaker and slower rise and faster drop of plasma insulin. The long action of oral and intravenous Hoe 490 in the dog can, however, not be sufficiently explained by the plasma insulin values. In the isolated rat pancreas perfused with glucose-free medium, HB 419 released glucagon beside insulin and somatostatin. The threshold concentration for the glucagon secretion was lower as those for the insulin and somatostatin release.(ABSTRACT TRUNCATED AT 250 WORDS)