Jpn. J. Pharmacol. 69, 251-258 (1995)

A Novel Adrenaline Derivative, AZ002, and Its Hypoglycemic Action in Yellow KK Mice

Yoshio Hioki, Yoshiki Itoh, Akira Nakajima, Takahiro Fukuroda, Hiroshi Ohasi, Toshio Kamei and Mitsuo Yano

Tsukuba Research Institute Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba 300-33, Japan

Abstract: AZ002 (L-threo-(3,4-dihydroxy phenyl)-N-methyl serine methyl ester) is a newly synthesized adrenaline derivative. AZ002 caused relaxation of rat jejunum (beta3-receptors) (ED50=18 microM), but did not affect the atrial rate (beta1) or tracheal relaxation (beta2) at a concentration of 0.3 mM. The pA2 values for propranolol in inhibiting the isoproterenol- and AZ002-stimulated relaxation of rat jejunum were 6.27 and 6.33, respectively. Thus, AZ002 is a selective agonist for beta3-adrenoceptor. AZ002 stimulated lipolysis (ED50=10 microM) and glucose uptake (ED50=1 microM) in rat adipocytes. In both cases, stimulation was antagonized by high concentrations of the beta-adrenoceptor antagonist propranolol, but not by the alpha- adrenoceptor antagonist phentolamine. The effect of AZ002 on glucose uptake was synergistic with that of insulin. AZ002 was also assessed in vivo by using genetically obese mice (KK/Ay strain) with hyperglycemia. Administration of AZ002 in the diet for a week decreased blood glucose and non-esterified fatty acids.

Keywords: AZ002, Adrenaline derivative, beta3-Adrenoceptor, Adipocyte

Copyright© The Japanese Pharmacological Society 1995

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