CD-832, a new dihydropyridine derivative with both nitrate-like and Ca2+ channel antagonist vasodilator activities

We investigated the effects of CD-832 ((4R)-(-)-2-(nicotinoylamino)ethyl 3-nitroxypropyl 1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate), a new dihydropyridine derivative with nitrate ester, on contraction and relaxation responses induced by various vasoactive agents in rabbit aorta. CD-832 potently inhibited the specific binding of [3H](+)-PN200-110 to rat brain membranes. The IC50 values for [3](+)-PN200-110 binding were 2.8 nM and 4.9 nM in CD-832 and nifedipine, respectively. CD-832 (10(-8) to 10(-5) M), diltiazem (10(-8) to 10(-5) M) and benidipine (10(-8) to 10(-5) M) inhibited the 64 mM KCl-induced contraction of the aortic strips in a concentration-dependent manner. Neither nitroglycerin (10(-8) to 10(-5) M) nor nicorandil (10(-8) to 10(-5) M) affected the 64 mM KCl-induced contraction in rabbit aorta. CD-832 (10(-8) to 10(-5) M), nitroglycerin (10(-8) to 10(-5) M) and nicorandil (10(-5) M) had no effect on norepinephrine-induced contraction in rabbit aorta. Nitroglycerin (10(-5) M), atrial natriuretic peptide (10(-8) M), nicorandil (10(-5) M) and CD-832 (10(-7) to 10(-5) M) augmented the isoproterenol-induced relaxation responses of rabbit aorta precontracted with endothelin-1 (1 x 10(-7) to 2 x 10(-7) M). The effects of nitroglycerin (10(-5) M), nicorandil (10(-5) M) and CD-832 (10(-5) M) on isoproterenol-induced relaxation responses were antagonized by treatment with methylene blue (10(-5) M) and oxyhemoglobin (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)