Effect of TC-81, a new dihydropyridine derivative, on K+-induced contraction in rat aorta

Abstract TC-81 (3-(N-benzyl-N-methylamino)-2,2-dimethylpropyl methyl-2,6-dimethyl-4-(2-fluoro-5-nitrophcnyl)-1,4-dihydro-pyridine-3,5-dicarboxylate hydrochloride) is a new dihydropyridine derivative. The effects of TC-81 (10 −10 –10 −8 M) on high K + -induced contractions were investigated in isolated rat aorta, and the results were compared with those obtained with nicardipine. nifedipine, diltiazem and papaverine. All drugs produced concentration-dependent relaxation of K + -induced contractions. The rate of relaxation induced by TC-81 was slower than that induced by the other drugs at concentrations producing the same final inhibition. However, the relaxing activity of TC-81 was 2.2, 16.7, 550 or 44000 times more potent than that of nicardipine, nifedipine, diltiazem or papaverine, respectively. The inhibitory effect of TC-81 was dependent on the duration of exposure to the agent and was antagonized when the external Ca 2+ concentration was raised. TC-81 concentration dependently inhibited La 3+ -resistant 45 Ca 2+ uptake in high K + solution. The data thus show that TC-81 produces a concentration-dependent and time-dependent Ca 2+ antagonistic action and that it is more potent than the other drugs tested.