SaRl 59-801 (59-801) (c-, is a novel, orally effective hypoglycemic compound which appears to act largely, if not entirely, by stimulation of insulin release. The compound is structurally unrelated to sulfonylurea derivatives.The 2-hr hypoglycemic EDz5 in fasting mice was 110 mglkg; the plasma insulin levels were increased, with an ED50 of 47 mglkg.Significant hypoglycemic activity was observed 2 hr after oral administration of 59-801 to fasting rats (ED25 = 86 mglkg), while plasma insulin was elevated by 62% at 100 mglkg. 59-801caused an insignificant decrease in plasma lactic acid levels. The hyperglycemic response 30 min after an oral starch load was inhibited by 1-hr pretreatment with 59-801 (ED5, = 37 mglkg). No tolerance to the hypoglycemic effect was observed after 28 days of dosing in rats.ln monkeys, the agent also produced hypoglycemia with a minimum effective dose of 10 mglkg and an ED25 of 33 mglkg for a period of 6 hr after oral administration. In genetically diabetic (db+ldb+) mice, 59-801 was more potent in producing hypoglycemia (ED25 = 47 mglkg) than their lean littermates (ED25 = 131 mglkg). In alloxan-diabetic rats or streptozotocin-diabetic mice, this agent was inactive at 200 mglkg, but at 400 mglkg, it caused reduction of blood glucose levels of 29-39 and 21%, respectively, possibly the result of stimulation of residual P-cell function. Thus far, stimulation of insulin release is the only mechanism found to explain the acute hypoglycemic activity of 59-801.