FR149175, a beta 3-adrenoceptor-selective agonist, is a possible therapeutic agent for non-insulin-dependent diabetes mellitus.
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 beta 3-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 FR149175 as well. These results suggest that FR149175 has antiobesity and antidiabetic effects and that this drug may be useful for treating NIDDM.
Yamamoto
H
H
Pharmacological Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Takakura
S
S
Yamamoto
T
T
Satoh
H
H
Higaki
M
M
Tomoi
M
M
Shimomura
K
K
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D002784:Cholesterol