[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.
Okamiya
Y
Y
Pharmaceutical Development Research Laboratories, Teijin Ltd., Tokyo, Japan.
Kishimoto
T
T
Aoki
K
K
Sunakawa
K
K
Hoshina
K
K
Takeshita
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014665:Vasodilator Agents; C074351:TC 81; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium