Binding of the new calcium entry blocker nilvadipine to rat aortic and guinea pig left ventricular membranes.
The binding of 3H-nilvadipine to the vascular (rat aortic) and cardiac (guinea pig left ventricular) microsomes was reversible and saturable. The results of the competitive binding experiments showed that nilvadipine had a higher affinity (Kd: 1.5 +/- 0.2 nmol/l) for the vascular binding sites than did nifedipine (Kd: 10.7 +/- 0.8 nmol/l) and nicardipine (Kd: 6.9 +/- 2.0 nmol/l), while the affinity of nilvadipine for the cardiac binding sites (Kd: 3.8 +/- 0.4 nmol/l) was similar to that of nifedipine (Kd: 3.3 +/- 0.1 nmol/l) and nicardipine (Kd: 4.2 +/- 0.3 nmol/l). The time courses of dissociation of the unlabeled dihydropyridines from the vascular binding sites were investigated using 3H-nitrendipine. Nilvadipine and nicardipine dissociated more slowly from the binding sites than did nifedipine. These results suggest that the high potency, selectivity for the vascular smooth muscle and long duration of action of nilvadipine may be related to its binding properties.
Product Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
M
M
Matsuo
Y
Y
Koibuchi
M
M
Tomoi
T
T
Ono
F
F
Shibayama
M
M
Ohtsuka
D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; C035100:nilvadipine; D009543:Nifedipine