Effect of the newly synthetized calcium antagonist isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5- dicarboxylate on cerebral venous outflow in dogs.

The effects of intravenous administration of isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydroyridi ne- 3,5-dicarboxylate (NB-818) on mean arterial blood pressure (MBP), heart rate (HR), cerebral blood flow (CBF), cerebral vascular resistance (CVR), arteriovenous oxygen difference (AVO2D), cerebral metabolic rate of oxygen (CMRO2) and blood gases were studied using the method of the cerebral venous outflow in dogs, and compared to those of nicardipine and nimodipine. 1. NB-818, nicardipine and nimodipine (1-10 micrograms/kg) decreased MBP dose-dependently accompanied by a decrease in HR only at doses of 10 micrograms/kg (NB-818) and 3-10 micrograms/kg (nimodipine). 2. NB-818 (1-10 micrograms/kg) increased CBF dose-dependently accompanied by a decrease in CVR. When comparing the potency or duration of action, the action of NB-818 showed a slower onset and was longer-lasting than that of nicardipine or nimodipine. 3. All three drugs (1-10 micrograms/kg) did not significantly affect CMRO2, AVO2D and blood gases (pH, pCO2 and pO2). These results indicate that the increase in CBF with NB-818 is longer in duration than that with nicardipine or nimodipine, and its effect is due to the dilatation of cerebral vessels. In addition, these results suggest that NB-818 is a potent cerebrovasodilator.