McN-3495, a new compound unrelated structurally to the sulfonylureas or phenformin, has been found to produce a hypoglycemic effect in nondiabetic rats, dogs, mice, and monkeys. The minimum effective dose of McN-3495 that lowers fasting blood glucose and improves glucose tolerance was found to be about 2.5 to 5 mg. per kilogram, per os, except in fasted monkeys, in which a tenfold greater potency was observed. When McN-3495 was given repeatedly for three to five days, no tolerance to the hypoglycemic activity occurred and no changes in other biochemical parameters were observed. In addition to being three to four times more potent than tolbutamide, McN-3495 also differs from the sulfonylureas in lowering blood glucose concentrations of streptozotocin-diabetic rats and db/db mice, and, moreover, oral administration to normal fasted dogs did not produce the characteristic rise in insulin concentrations observed with tolbutamide. Furthermore, unlike the biguanides, McN-3495 can lower dog and rat fasting blood glucose concentrations and can improve glucose tolerance whether the glucose is administered orally or parenterally. However, McN-3495, as phenformin, fails to work in totally depancreatized dogs.

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