1986 年 41 巻 4 号 p. 459-466
The pharmacological activities of the enantiomers of amosulalol (YM-09538), a combined α- and β-adrenoceptor antagonist, and the corresponding desoxy derivative (YM-11133) were investigated in the cardiovascular system of rats. The optical isomers of amosulalol and YM-11133 antagonized the vasopressor effect of phenylephrine and the positive chronotropic effect of isoproterenol in normotensive pithed rats. Based on DR2 values (μg/kg, i.v.) obtained from Schild plots, (+)-amosulalol and YM-11133 (DR2=30) were approximately 10 times more potent than (-)-amosulalol (DR2=324) in blocking α1-adrenoceptors. For β1-adrenoceptors, in contrast, (-)-amosulalol (DR2=107) was approximately 60 times more potent than (+)-amosulalol (DR2=6460), which was almost equipotent with YM-1 1133 (DR2=3250). The results indicate that the optical isomers of amosulalol interact differently with α- and β-adrenoceptors. The effects of these phenethylamines on blood pressure and heart rate were studied in urethaneanesthetized rats (i.v.). The rank order of hypotensive potency in anesthetized rats ((+)-=desoxy>(-)-form) was consistent with the rank order of α1-adrenoceptor antagonism in pithed rats. In contrast, (-)-amosulalol having a more potent β1-adrenoceptor antagonist activity than (+)-amosulalol and YM-11133 only produced dose-dependent bradycardia at the hypotensive doses. The results indicate that the vascular α1- and cardiac β1 -adrenoceptor blocking activities of the optical isomers of amosulalol contribute to their hypotensive and bradycardia, respectively. Thus, the racemate of amosulalol appears to exert an overall activity reflecting the activities of the individual isomers.
