Hemodynamic effects of a dihydropyridine calcium antagonist, NB-818 (NPK-1886) in anesthetized dogs.
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.
Nishikibe
M
M
Central Research Laboratories, Banyu Pharmaceutical Co. Ltd., Tokyo, Japan.
Nagura
J
J
Kamei
K
K
Fukuroda
T
T
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009553:Nimodipine; C048962:NPK 1886; D009529:Nicardipine; D009543:Nifedipine