Antihypertensive effects of a new dihydropyridine calcium antagonist.
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.
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002415:Cats; D004095:Dihydropyridines; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000188:drug therapy; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010991:Plethysmography; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013045:Species Specificity
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009943:Organophosphorus Compounds; D011725:Pyridines; C050266:DHP 218; D009543:Nifedipine