EFFECTS OF THE NOVEL WATER-SOLUBLE CALCIUM-ANTAGONIST (+ -)-3-(4-ALLYL-1-PIPERAZINYL)-2,2-DIMETHYLPROPYL METHYL METHYL-4-(3-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLATE DIHYDROCHLORIDE ON THE ENDOTHELIUM-INDEPENDENTAND ENDOTHELIUM-DEPENDENT CONTRACTION IN ISOLATED CANINE CEREBRAL-ARTERIES/

The inhibitory effects of NKY-722 (+/-)-3-(4-allyl-1-piperazinyl)-2,2- dimethylpropyl methyl methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxyla te dihydrochloride, CAS 117241-46-0) on endothelium-independent and en dothelium-dependent contractions were examined in comparison with nica rdipine in isolated canine cerebral arteries. NKY-722 relaxed the cere bral arteries contracted endothelium Independently by KCl, prostagland in F-2 alpha U-46619 (a thromboxane A(2) agonist) and endothelin-1 wit h IC50 = 2.5, 3.4, 2.8 and 3.6 x 10(-10) mol/l, respectively. On the b asis of IC50 values, NKY-722 was about 2 times more effective than nic ardipine. Pretreatment of NKY-722 and nicardipine inhibited the endoth elium-independent contraction induced by KCl and serotonin to a simila r degree. NKY-722 attenuated the endothelium-dependent contractions ca used by acetylcholine (ACh), adenosine diphosphate and KO2 with IC50 = 1.7, 3.8 and 1.4 x 10(-9) mol/l, respectively. NKY-722 was about 2 ti mes less effective than nicardipine. NKY-722 and nicardipine inhibited dose-dependently the endothelium-dependent contractions induced by he molysate. NKY-722 was nearly equipotent to nicardipine on the phasic c ontraction and slightly more potent on the tonic contraction. The inhi bitory effect of NKY-722 on the endothelium-independent contraction in duced by KCl and the endothelium-dependent contraction induced by ACh were sustained for a longer time than that of nicardipine after repeti tive wash-out. In conclusion, NKY-722 inhibited effectively the endoth elium-independent and endothelium-dependent contractions in the cerebr al arteries. The effect of NKY-722 was similar to, but longer-lasting than that of nicardipine.