Effect of palonidipine hydrochloride (TC-81), a novel calcium antagonist, on the canine coronary artery

The effects of palonidipine hydrochloride [TC-81: (±)-3-benzylmethylamino)-2, 2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1, 4-dihydro-2, 6-dimethyl-3, 5-pyridinedicarboxylate hydrochloride], a new calcium antagonist, on the coronary artery were studied in dogs. In the isolated canine coronary artery, TC-81 inhibited high K+ (60 mM)-induced contraction in a concentration-dependent manner. The relaxant activity of TC-81 was equal to that of nicardipine and more potent than those of nifedipine and diltiazem. TC-81 increased coronary blood flow in a dose-dependent manner after i.v.-administration in anesthetized open-chest dogs. The activity of TC-81 was equal to that of nifedipine or nicardipine, but the duration of its effect was longer than that of nifedipine or nicardipine. By oral administration in conscious dogs, TC-81 increased coronary blood flow at 0.1 mg/kg or more, and its activity was 10 times more potent than that of nifedipine. These results suggest that TC-81 increases coronary blood flow and is capable of improving the oxygen supply-demand relationship during angina pectoris.