Effects of the new calcium antagonist 2-nitratopropyl-3-nitratopropyl-2,6-dimethyl-4-(3-nitrophe nyl)- 1,4-dihydropyridine-3,5-dicarboxylate on cerebral circulation in dogs.

2-Nitratopropyl-3-nitratopropyl-2,6-dimethyl-4-(3-nitropheny l)- 1,4-dihydropyridine-3,5-dicarboxylate (CD-349), nimodipine and nicardipine (0.3-3 micrograms/kg i.v.) increased vertebral blood flow (VBF) in the anesthetized dog, the effect of CD-349 being the strongest, and they also decreased blood pressure. All these drugs slightly increased femoral blood flow. CD-349, nimodipine and nicardipine (1-10 micrograms/kg i.v.) increased cerebral tissue blood flow (CBF) in the anesthetized dog, CD-349 producing the most sustained and pronounced effect. CD-349 (3 micrograms/kg i.v.) restored the decrease of CBF induced by the application of 0.5 ml of serotonin (5-HT, 10(-5) mol/l), KCl (30 mmol/l) and prostaglandin F2 alpha (PGF2 alpha, 10(-4) mol/l) to the surface of the cerebrum of the anesthetized dog. In isolated canine basilar arteries. K-contraction was completely inhibited, but the relaxation of 5-HT- and PGF2 alpha-contractions by these drugs was incomplete. CD-349 had a more potent effect than nicardipine and nimodipine on basilar arteries. These results indicate that CD-349 is a potent cerebrovasodilator.