The effects of
NB-818, isopropyl methyl 2-carbamoyloxy-methyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihyd rop yridine-3,5-dicarboxylate, on the cardiovascular system were investigated in comparison with those of
nicardipine and
nimodipine, using anesthetized dogs. 1)
NB-818 1-20 micrograms/kg intravenously (i.v.),
nicardipine 0.3-10 micrograms/kg i.v. and
nimodipine 0.3-10 micrograms/kg i.v. decreased mean arterial blood pressure (MBP), total peripheral resistance (TPR) and renal blood flow (RBF) and increased cardiac output (CO) and stroke volume (SV), but did not affect heart rate (HR) and PQ-interval. 2)
NB-818 1-20 micrograms/kg i.v. increased vertebral blood flow (VBF) dose-dependently, with a moderate decrease of MBP and little or no change in HR or femoral blood flow (FBF). Both
nicardipine 0.3-10 micrograms/kg i.v. and
nimodipine 0.3-10 micrograms/kg i.v. not only increased VBF in a dose-dependent manner, but also markedly decreased MBP and tended to increase FBF. The increase in VBF with
NB-818 was a little less than that with
nicardipine and
nimodipine, but its effect was significantly slower in onset and of longer duration as compared to
nicardipine and
nimodipine. 3) The ratio of decrease of vertebral vascular resistance (VR) to decrease of TPR was significantly larger with
NB-818 and
nimodipine than with
nicardipine. 4)
NB-818,
nicardipine and
nimodipine in a range of 0.3-10 micrograms intraarterially (i.a.) increased VBF, and the effect of
NB-818 was longer lasting than that of
nicardipine and
nimodipine. 5)
NB-818 0.003-0.1 mg/kg intraduodenally (i.d.) also caused a longer lasting increase in VBF with a slower onset that was accompanied by moderate
hypotension and was dose-dependent. The duration of action was significantly longer than that of
nimodipine 0.1-0.3 mg/kg i.d. Thus,
NB-818 predominantly increases VBF with concomitant moderate
hypotension, and its action is of significantly slower onset and longer duration than that of
nicardipine and
nimodipine.