Relationship between tissue content of TC-81 and relaxation of rat aorta.
This study dealt with the relationship between the relaxant action of TC-81, a new Ca2+ antagonist, and its distribution in rat aorta depolarized by high K+ (65.4 mM). The inhibitory effect by TC-81 on K(+)-induced contraction and 45Ca2+ uptake was strongly time-dependent. TC-81 and nicardipine, each 10(-9) M, produced gradual relaxation of high-K(+)-induced contraction. The tissue contents of TC-81 and nicardipine increased with time courses that reflected decreasing tension. Both the maximum tissue content of TC-81 and the maximum relaxation were significantly greater than those for nicardipine. Also, the relaxations produced by TC-81 and nicardipine were correlated with the logarithm of the content of each drug in muscle tissues. However, the dissociation of TC-81 from the tissues was slower than that of nicardipine. The data suggest that the action of TC-81 is closely related to a gradual distribution of drug into muscle tissue, resulting in a slow onset of action. Also, the saturation time of TC-81 was longer than that of nicardipine, thereby accounting for the greater relaxation with TC-81.
Okamiya
Y
Y
Pharmacological Research Department, Teijin Institute for Bio-Medical Research, Tokyo, Japan.
Kishimoto
T
T
Aoki
K
K
Tanabe
H
H
Takeshita
T
T
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology; D002132:Calcium Radioisotopes; D004095:Dihydropyridines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014665:Vasodilator Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D004095:Dihydropyridines; D014665:Vasodilator Agents; C074351:TC 81; D011188:Potassium; D002118:Calcium