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目的测定外消旋TJ0711(R/S-)及其两种旋光异构体(S-和R-)对肾上腺素受体各亚型拮抗作用的强度及相对选择性。方法采用离体器官实验法,以离体豚鼠右心房、气管条、离体大鼠肛尾肌、输精管为标本分别测定受试物对β1和β2,α1和α2肾上腺素受体的拮抗参数(pA2)。结果R/S-、S-及R-TJ0711拮抗β1受体的pA2值分别为:7.35、7.22和7.17;拮抗β2受体的pA2值分别为:6.24、6.11和6.23;拮抗α1受体的pA2值分别为:7.63、7.37和7.33;拮抗α2受体的pA2值分别为:5.70、6.08和5.64。S-和R-TJ0711对4种肾上腺素受体亚型的pA2值差异无显著性。R/S-TJ0711拮抗α1受体的pA2值高于S-和R-TJ0711;对另外3种受体亚型,R/S-TJ0711与拆分体的pA2值差异无显著性。结论在离体器官实验中,S-、R-TJ0711对肾上腺素受体各亚型的拮抗作用无明显差异,二者在拮抗α1受体时表现出协同作用;R/S-、S-和R-TJ0711对β1和α1受体的选择性较高。
Objective To determine the intensity and relative selectivity of racemic TJ0711 (R / S-) and its two optical isomers (S- and R-) on the antagonism of adrenergic receptor subtypes. Methods The isolated organ test was used to determine the antagonistic parameters of β1 and β2, α1 and α2 adrenoceptors in isolated right atrium, tracheal strips, isolated rodent tail muscle and vas deferens in vitro pA2). Results The pA2 values of antagonist β1 receptor of R / S-, S- and R-TJ0711 were 7.35, 7.22 and 7.17, respectively; the pA2 values of antagonist β2 receptor were 6.24, 6.11 and 6.23, respectively; pA2 antagonizing α1 receptor Values were 7.63, 7.37 and 7.33, respectively; pA2 values for antagonizing α2 receptors were 5.70, 6.08 and 5.64, respectively. There was no significant difference in the pA2 values of the four adrenergic receptor subtypes between S- and R-TJ0711. The pA2 value of R / S-TJ0711 antagonizing α1 receptor was higher than that of S- and R-TJ0711. For the other three receptor subtypes, the pA2 value of R / S-TJ0711 and the split body was not significantly different. CONCLUSIONS: In vitro experiments, there was no significant difference in the antagonism of S- and R-TJ0711 between adrenergic receptor subtypes. Both of them showed synergistic effect on the antagonism of α1 receptor. R / S-, S- and R-TJ0711 has a high selectivity for β1 and α1 receptors.