Hypotensive effect of l-(2,6-dimethylphenoxy)-2-(3,4-dimethoxy-phenylethylamino) propane hydrochloride

l-( 2, 6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride (D) was synthesized by Nanjing College of Pharmacy according to the structural characteristic of mexiletine. The influence of D on blood pressure of rats and possible mechanism were studied. D 3, 10 mg/kg iv lowered mean arterial pressure in pentobarbiton-anaesthetized normotensive rats, conscious normotensive rats and conscious renal hypertensive rats. In pithed rats pretreated with D 3, 10 mg/kg shifted log dose-response curve of methoxamine to the right in parallel manner but D 10 mg/kg reduced the maximal response of B-HT 920. In rabbit aorta, portal vein and rat anococcygeus muscle D 0.1, 0.3, 1 vmol/L shifted methoxamine cumulative dose-response curves rightward parallelly with pAz values of 7.15, 6.92 and 7.32, respectively. D inhibited the contraction evoked by KC1 40 mmol/L in rabbit aorta with a IC50 value of 93 Umol/L. The dase-response curve for clonidine to inhibit electrical stimulation-evoked contraction of the prostatic portion of rat vas deferens was shifted rightward parallejly by D 30, 100 vmol/L with a pAz value of 5.1. These results suggest that D can block al- and az-adrenoceptors. The selective ratio for D to block aiadrenoceptors in anococcygeus muscje and az-adrenoceptors in vas deferens from the same rat (ai/az) was 162. Possibly, D also possesses a calcium antagonistic effect.