FR149175, a beta(3)-adrenoceptor-selective agonist, is a possible therapeutic agent for non-insulin-dependent diabetes mellitus

被引:14
作者
Yamamoto, H
Takakura, S
Yamamoto, T
Satoh, H
Higaki, M
Tomoi, M
Shimomura, K
机构
[1] Pharmacol. Research Laboratories, Fujisaw Pharmaceutical Co., Ltd., Yodogawa-ku, Osaka 532
关键词
FR149175; beta(3)-adrenoceptor; non-insulin-dependent diabetes mellitus (NIDDM);
D O I
10.1254/jjp.74.109
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 (AUG) 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.
引用
收藏
页码:109 / 112
页数:4
相关论文
共 11 条
[1]   THE HUMAN BETA-3-ADRENOCEPTOR - THE SEARCH FOR A PHYSIOLOGICAL-FUNCTION [J].
EMORINE, L ;
BLIN, N ;
STROSBERG, AD .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1994, 15 (01) :3-7
[2]   MOLECULAR CHARACTERIZATION OF THE HUMAN BETA-3-ADRENERGIC RECEPTOR [J].
EMORINE, LJ ;
MARULLO, S ;
BRIENDSUTREN, MM ;
PATEY, G ;
TATE, K ;
DELAVIERKLUTCHKO, C ;
STROSBERG, AD .
SCIENCE, 1989, 245 (4922) :1118-1121
[3]   DEMONSTRATION OF AN IN-VIVO FUNCTIONAL BETA(3)-ADRENOCEPTOR IN MAN [J].
ENOCKSSON, S ;
SHIMIZU, M ;
LONNQVIST, F ;
NORDENSTROM, J ;
ARNER, P .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (05) :2239-2245
[4]   TISSUE DISTRIBUTION OF BETA-3-ADRENERGIC RECEPTOR MESSENGER-RNA IN MAN [J].
KRIEF, S ;
LONNQVIST, F ;
RAIMBAULT, S ;
BAUDE, B ;
VANSPRONSEN, A ;
ARNER, P ;
STROSBERG, AD ;
RICQUIER, D ;
EMORINE, LJ .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (01) :344-349
[5]   INVIVO HEPATIC AND PERIPHERAL INSULIN RESISTANCE IN GENETICALLY-OBESE (FA FA) RATS [J].
TERRETTAZ, J ;
JEANRENAUD, B .
ENDOCRINOLOGY, 1983, 112 (04) :1346-1351
[6]   TIME OF ONSET OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS AND GENETIC-VARIATION IN THE BETA(3)-ADRENERGIC-RECEPTOR GENE [J].
WALSTON, J ;
SILVER, K ;
BOGARDUS, C ;
KNOWLER, WC ;
CELI, FS ;
AUSTIN, S ;
MANNING, B ;
STROSBERG, AD ;
STERN, MP ;
RABEN, N ;
SORKIN, JD ;
ROTH, J ;
SHULDINER, AR .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (06) :343-347
[7]  
YAMAGUNI H, 1996, FOLIA PHARMACOL JPN, V107, pP48
[8]   ANTIOBESITY EFFECT OF CL-316,243, A HIGHLY SPECIFIC BETA(3)-ADRENOCEPTOR AGONIST, IN MICE WITH MONOSODIUM-L-GLUTAMATE-INDUCED OBESITY [J].
YOSHIDA, T ;
SAKANE, N ;
WAKABAYASHI, Y ;
UMEKAWA, T ;
KONDO, M .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 1994, 131 (01) :97-102
[9]  
YOSHIDA T, 1991, ENDOCRINOL JAPON, V38, P641
[10]   ANTIOBESITY AND ANTIDIABETIC EFFECTS OF CL-316,243, A HIGHLY SPECIFIC BETA(3)-ADRENOCEPTOR AGONIST, IN YELLOW KK MICE [J].
YOSHIDA, T ;
SAKANE, N ;
WAKABAYASHI, Y ;
UMEKAWA, T ;
KONDO, M .
LIFE SCIENCES, 1994, 54 (07) :491-498