Effects of the novel water-soluble calcium antagonist (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride on the endothelium-independent and endothelium-dependent contraction in isolated canine cerebral arteries.

The inhibitory effects of NKY-722 (±)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride, CAS 117241-46-0) on endothelium-independent and endothelium-dependent contractions were examined in comparison with nicardipine in isolated canine cerebral arteries. NKY-722 relaxed the cerebral arteries contracted endothelium-independently by KCl, prostaglandin F 2α U-46619 (a thromboxane A 2 agonist) and endothelin-l with IC 50 = 2.5, 3.4, 2.8 and 3.6 x 10 -10 mol/l, respectively. On the basis of IC 50 values, NKY-722 was about 2 times more effective than nicardipine. Pretreatment of NKY-722 and nicardipine inhibited the endothelium-independent contraction induced by KCI and serotonin to a similar degree. NKY-722 attenuated the endothelium-dependent contractions caused by acetylcholine (ACh), adenosine diphosphate and KO 2 with IC 50 = 1.7, 3.8 and 1.4 x 10 -9 mol/l, respectively. NKY-722 was about 2 times less effective than nicardipine. NKY-722 and nicardipine inhibited dose-dependently the endothelium-dependent contractions induced by hemolysate. NKY-722 was nearly equipotent to nicardipine on the phasic contraction and slightly more potent on the tonic contraction. The inhibitory effect of NKY-722 on the endothelium-independent contraction induced by KCl and the endothelium-dependent contraction induced by ACh were sustained for a longer time than that of nicardipine after repetitive wash-out. In conclusion, NKY-722 inhibited effectively the endothelium-independent and endothelium-dependent contractions in the cerebral arteries. The effect of NKY-722 was similar to, but longer-lasting than that of nicardipine.