Y. Hioki et al., A NOVEL ADRENALINE DERIVATIVE, AZ002, AND ITS HYPOGLYCEMIC ACTION IN YELLOW KK MICE, Japanese Journal of Pharmacology, 69(3), 1995, pp. 251-258
AZ002 (L-threo-(3,4-dihydroxy phenyl)-N-methyl serine methyl ester) is
a newly synthesized adrenaline derivative. AZ002 caused relaxation of
rat jejunum (beta(3)-receptors) (ED(50) = 18 mu M), but did not affec
t the atrial rate (beta(1)) or tracheal relaxation (beta(2)) at a conc
entration of 0.3 mM. The pA(2) values for propranolol in inhibiting th
e isoproterenol- and AZ002-stimulated relaxation of rat jejunum were 6
.27 and 6.33, respectively. Thus, AZ002 is a selective agonist for bet
a(3)-adrenoceptor. AZ002 stimulated lipolysis (ED(50) = 10 mu M) and g
lucose uptake (ED(50) = 1 mu M) in rat adipocytes. In both cases, stim
ulation was antagonized by high concentrations of the beta-adrenocepto
r antagonist propranolol, but not by the alpha-adrenoceptor antagonist
phentolamine. The effect of AZ002 on glucose uptake was synergistic w
ith that of insulin. AZ002 was also assessed in vivo by using genetica
lly obese mice (KK/Ay strain) with hyperglycemia. Administration of AZ
002 in the diet for a week decreased blood glucose and non-esterified
fatty acids.