Callaway J K, King R G, Boura A L
Department of Pharmacology, Manash University, Clayton, Victoria, Australia.
Arch Int Pharmacodyn Ther. 1990 Nov-Dec;308:86-94.
Measurements were made of the effects of methoxyphenamine hydrochloride on histamine-, acetylcholine- and U46619-induced bronchoconstriction in pentobarbitone-anaesthetized guinea-pigs, and on histamine- and acetylcholine-induced contractions of guinea-pig ileum in vitro. Methoxyphenamine (20 mg/kg, i.v.) did not affect bronchoconstriction induced by acetylcholine or the thromboxane A2-mimetic U46619. However, it produced a parallel rightward shift [2.94-(1.79, 4.41) fold, 95% confidence limits in parentheses] of the curve relating bronchoconstrictor responses to log-dose of histamine at a total dose of 13 mg/kg, i.v., which was not significantly different from the shift [3.30-(1.93, 5.56) fold] produced by 3 micrograms/kg, i.v., of the histamine antagonist mepyramine maleate. Histamine-induced contractions of the isolated guinea-pig ileum were antagonized by methoxyphenamine (10(-5) to 10(-3) M). The histamine log-concentration-response curve was shifted to the right in a parallel manner by methoxyphenamine (10(-5) to 10(-4) M), without depression of maximum responses. However, at higher concentrations, maximum responses were reduced. The slope of the Schild plot was significantly different from -1. The degree of the rightward shift of the concentration-response curves to histamine, produced by 10(-5) M of methoxyphenamine [3.90-(2.83, 4.97) fold], was not significantly different from that produced by 3 x 10(-9) M of mepyramine [4.60-(2.86, 6.52) fold]. Methoxyphenamine, at concentrations of 10(-5) to 3 x 10(-4) M, had no significant effect on responses of guinea-pig ilea to acetylcholine (10(-9) to 10(-5) M). These results indicate that methoxyphenamine antagonizes the effects of histamine both in vivo and in vitro. In vitro studies indicate a noncompetitive antagonism.
测定了盐酸甲氧那明对戊巴比妥麻醉的豚鼠体内组胺、乙酰胆碱和U46619诱导的支气管收缩的影响，以及对体外豚鼠回肠组胺和乙酰胆碱诱导的收缩的影响。静脉注射20mg/kg的甲氧那明对乙酰胆碱或血栓素A2模拟物U46619诱导的支气管收缩没有影响。然而，静脉注射总剂量为13mg/kg时，它使支气管收缩反应与组胺对数剂量关系曲线平行右移[2.94-(1.79, 4.41)倍，括号内为95%置信限]，这与静脉注射3μg/kg组胺拮抗剂马来酸氯苯那敏产生的右移[3.30-(1.93, 5.56)倍]无显著差异。体外实验中，10(-5)至10(-3)M的甲氧那明可拮抗组胺诱导的豚鼠离体回肠收缩。10(-5)至10(-4)M的甲氧那明使组胺对数浓度-反应曲线平行右移，而最大反应未降低。然而，在较高浓度时，最大反应降低。Schild图的斜率显著不同于-1。10(-5)M的甲氧那明使组胺浓度-反应曲线右移的程度[3.90-(2.83, 4.97)倍]与3×10(-9)M的氯苯那敏产生的右移[4.60-(2.86, 6.52)倍]无显著差异。浓度为10(-5)至3×10(-4)M的甲氧那明对豚鼠回肠对乙酰胆碱(10(-9)至10(-5)M)的反应无显著影响。这些结果表明，甲氧那明在体内和体外均能拮抗组胺的作用。体外研究表明其为非竞争性拮抗作用。
