ANTIHYPOTENSIVE EFFECT OF THE NOVEL WATER-SOLUBLE CALCIUM-ANTAGONIST (+ -)-3-(4-ALLYL-1-PIPERAZINYL)-2,2-DIMETHLYPROPYL METHYL METHYL-4-(3-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLATE DIHYDROCHLORIDE IN RATS/

The antihypertensive effect of (+/-)-3-(4-allyl-1-piperazinyl)- -2,2-d imethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl)-3,5-p yridinedicarboxylate dihydrochloride (NKY-722, CAS 117241-46-0) was ex amined in conscious spontaneously hypertensive rats (SHR), normotensiv e Wistar rats (NWR) and anesthetized NWR, and its vasodilatory effect was investigated in the perfused NWR mesenteric vascular bed NKY-722 a nd nicardipine administered intravenously (10-100 mu g/kg) and orally (0.3-10 mg/kg) lowered blood pressure dose-dependently with an increas e in heart rate in conscious SHR and NWR. The effects of NKY-722 were slower in onset and longer-lasting than those of nicardipine, and were more marked in SHR than in NWR. The effect of NKY-722 was roughly the same as that of nicardipine on intravenous administration. However, N KY-722 was 4-8 times more potent than nicardipine on oral administrati on. In anesthetized NWR, the hypotensive effects of NKY-722 administer ed via the femoral vein, portal vein and duodenum were examined in com parison with those of nicardipine. The findings suggest that NKY-722 i s more efficiently absorbed from the gastro-intestinal tract and more resistant to the hepatic first pass effect than nicardipine. In the pe rfused NWR vascular bed NKY-722 and nicardipine (0.01-1.0 mu g) attenu ated the pressor response to KCl dose-dependently, The effect of NKY-7 22 was slower in onset and longer-lasting than that of nicardipine. In conclusion; NKY-722 has a potent, slow-onset and long-lasting antihyp ertensive activity which is mainly attributed to its slow-onset and lo ng-lasting vasodilatory action. NKY-722 is expected to be a useful ant ihypertensive drug.