[Effect of amlodipine, a new calcium antagonist on isolated blood vessels].
Amlodipine (AML), a new 1,4-dihydropyridine derivative, similar to nifedipine (NIF), dose-dependently relaxed or inhibited the KCL-contraction (cont.) of dog coronary artery (DCA) and rat aorta (RA) and the spontaneous motility of rat portal vein (RPV). However, in contrast to the case of NIF, the maximum effect was obtained at 1-2 hr following an addition of AML, and the recovery of KCl-cont. after removal of AML was very slow. Similar effects of AML on KCl-cont. were observed in dog femoral artery (DFA), dog basilar artery (DBA) and rabbit aorta (RBA). The IC50 values of AML for producing the half-maximal effect were 6.5 x 10(-9) M, 6.5 x 10(-9) M, 1.1 x 10(-8) M, 1.7 x 10(-8) M and 4.8 x 10(-8) M in DCA, DFA, RPV, DBA and RBA, respectively. In these vessels, the potency of AML was slightly less than the potency of NIF. On the other hand, AML (10(-7), 10(-6) M) only slightly attenuated norepinephrine (NE)-induced cont. in DFA and RA. Based on the ratio of IC50 values in DFA, AML exhibited 846-fold higher selectivity toward KCl-cont. than NE-cont., and it was much higher than the selectivity of NIF. In calcium-free medium, AML failed to inhibit the NE-cont. in RA, but it markedly inhibited CaCl2-induced cont. These results indicate that AML significantly inhibits KCl-cont. in blood vessels at lower doses with slightly less potency than NIF, but with a higher selectivity than NIF in comparison with the potency against NE-cont., and they also confirmed that the effect of AML is of slow onset and long-lasting.
Yamanaka
K
K
Pharmacology Laboratory, NPDC, Pfizer Pharmaceuticals Inc., Aichi, Japan.
Suzuki
M
M
Munehasu
S
S
Ishiko
J
J
D017311:Amlodipine; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000037:antagonists & inhibitors; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; 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; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D017311:Amlodipine; D011189:Potassium Chloride; D009543:Nifedipine; D002122:Calcium Chloride; D009638:Norepinephrine