Abstract
We examined whether FR149175 (ethyl-[(S)-8-[(R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yloxy]acetate monohydrochloride monohydrate), a selective agonist for the β3-adrenoceptor, is a possible therapeutic agent for non-insulin-dependent diabetes mellitus (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 hyperinsulinemia and showed a tendency to decrease the area under the curve (AUC) for plasma glucose levels in the glucose tolerance test. Moreover, FR149175 decreased plasma triglyceride, free fatty acid and total cholesterol levels in the rats. Body weight gain in the rat was suppressed by FRI49175 as well. These results suggest that FRI49175 has antiobesity and antidiabetic effects and that this drug may be useful for treating NIDDM.
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