FR149175, A BETA(3)-ADRENOCEPTOR-SELECTIVE AGONIST, IS A POSSIBLE THERAPEUTIC AGENT FOR NON-INSULIN-DEPENDENT DIABETES-MELLITUS

We examined whether FR149175 (R)-2-(3-chlorophenyl)-2-hydroxyethylamin o]-6,7,8, 9-tetrahydro-5H-benzocyclohepten-2-yloxy] acetate monohydroc hloride monohydrate), a selective agonist for the beta(3)-adrenoceptor , is a possible therapeutic agent for non-insulin-dependent diabetes m ellitus (NIDDM). FR149175 had hypoglycemic effects with an increase in the level of plasma insulin in normal rats. In Zucker fatty rats, an animal model of NIDDM, repeated administration of the drug improved hy perinsulinemia and showed a tendency to decrease the area under the cu rve (AUG) for plasma glucose levels in the glucose tolerance test. Mor eover, FR149175 decreased plasma triglyceride, free fatty acid and tot al cholesterol levels in the rats. Body weight gain in the rat was sup pressed by FR149175 as well. These results suggest that FR149175 has a ntiobesity and antidiabetic effects and that this drug may be useful f or treating NIDDM.