Kimura Y, Fukui H, Tanaka M, Okamoto M, Morino A, Miura A, Kimura K, Enomoto H
Arzneimittelforschung. 1986 Sep;36(9):1329-35.
Methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2 -yl)-1,4-dihydropyridine-3-carboxylate (DHP-218) is a new vasodilatory calcium antagonist with pronounced and long-lasting antihypertensive effects. It produced a significant decrease in blood pressure at doses more than 1 mg/kg in normotensive rats, 0.1 mg/kg in spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)-salt hypertensive rats and 0.3 mg/kg in renal hypertensive rats. In SHR, the antihypertensive effect of DHP-218 was approximately 7 times more potent than nifedipine. The antihypertensive effect of DHP-218 appeared very slowly and persisted even after it was injected i.v. No tolerance to the antihypertensive effects of DHP-218 was observed for 5 weeks at daily doses of 0.3 and 1 mg/kg. The antihypertensive effects of DHP-218 in cats and dogs with normal blood pressure was more than 10 and 30 times more potent than those of nifedipine, respectively. At an equivalent antihypertensive dose, the effect of DHP-218 persisted longer than that of nifedipine in all the animal species used.
2,6 - 二甲基 - 4 - (2 - 硝基苯基) - 5 - (2 - 氧代 - 1,3,2 - 二氧磷杂环己烷 - 2 - 基) - 1,4 - 二氢吡啶 - 3 - 羧酸甲酯（DHP - 218）是一种新型血管舒张性钙拮抗剂，具有显著且持久的降压作用。在正常血压大鼠中，剂量超过1mg/kg时可使血压显著降低；在自发性高血压大鼠（SHR）、醋酸脱氧皮质酮（DOCA）盐性高血压大鼠中，剂量为0.1mg/kg时可使血压显著降低；在肾性高血压大鼠中，剂量为0.3mg/kg时可使血压显著降低。在SHR中，DHP - 218的降压作用比硝苯地平强约7倍。DHP - 218的降压作用出现非常缓慢，静脉注射后仍持续存在。每日剂量为0.3mg/kg和1mg/kg时，连续5周未观察到对DHP - 218降压作用的耐受性。DHP - 218对正常血压猫和犬的降压作用分别比硝苯地平强10倍和30倍以上。在等效降压剂量下，DHP - 218在所有使用的动物物种中的作用持续时间均比硝苯地平长。
