1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐对大鼠心脏α_1受体的影响

Effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxy-phenylethylamino) propane hydrochloride on cardiac α1-adrenoceptor of rats

DDPH 3 mg/kg对毁脊髓大鼠有拮抗甲氧胺升高左心室压力及室内压最大变化速率(±dP/dt_(max))、左室舒张末期压、血压和心率的作用;在大鼠离体工作心脏上,有普萘洛尔存在时,DDPH 1～10μmol/L有阻断苯福林升高左心室压力及dP/dt_(max)、主动脉流量和心率的作用;DDPH60μmol/L灌流大鼠在体心肺,有取消甲氧明提高左心室压力和心输出量的作用。DDPH尚可显著减慢大鼠工作心脏和在体心肺装置的心率。上述结果提示DDPH对血管平滑肌及心肌的α_1受体有阻断作用。

1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride(DDPH)was synthesized by China University of Pharmacy according to the structural characteristic of mexiletine.In pithed rats,α1-adrenoceptor agonist me-thoxamine(30-300μg/kg,iv)dose-dependently increased LVP,±dP/dtmax,LVEDP,SAP and DAP.The changes in haemodynamics induced by iv methoxamine-could be antagonized by DDPH(3 mg/kg)and prazosin(0.1 mg/kg).The increase in HR induced by iv methoxamine(300μg/kg)could also be antagonized by pretreatment with DDPH and prazosin.In the rat's working heart,phenylephrine(30μmol/L)in the presence of propranolol(0.1μmol/L)increased LVP,±dP/dtmax,ABF and HR,which were antagonized by pretreatment with DDPH(1-10μmol/L)and prazosin(0.1μmol/L).DDPH(1-10μmol/L)could significantly decrease HR in the isolated rat's working heart,which was different from prazosin.In the rat heart-lung preparation in vivo,DDPH(60μmol/L)could block the methoxamine-induced increases in LVP and CO whereas the decrease in HR produced by DDPH was not affected by methoxamine.The results suggest that DDPH is able to block α1-adrenoceptors not only in vascular smooth muscles,but also in rat myocardium.