Effect of TC-81, a new dihydropyridine derivative, on K(+)-induced contraction in rat aorta.
TC-81 (3-(N-benzyl-N-methylamino)-2,2-dimethylpropyl methyl-2,6-dimethyl-4-(2-fluoro-5-nitrophenyl)-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 44,000 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 Ca2+ concentration was raised. TC-81 concentration dependently inhibited La(3+)-resistant 45Ca2+ uptake in high K+ solution. The data thus show that TC-81 produces a concentration-dependent and time-dependent Ca2+ antagonistic action and that it is more potent than the other drugs tested.
Okamiya
Y
Y
Pharmacological Research Department, Teijin Institute for Bio-Medical Research II, Tokyo, Japan.
Kishimoto
T
T
Aoki
K
K
Tanabe
H
H
Takeshita
T
T
Naruchi
T
T
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002132:Calcium Radioisotopes; D004095:Dihydropyridines / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002132:Calcium Radioisotopes; D004095:Dihydropyridines; D014665:Vasodilator Agents; C074351:TC 81; D009529:Nicardipine; D010208:Papaverine; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium; D002118:Calcium