In vitro effects of the new calcium antagonist lacidipine.
The effects of lacidipine (LC), a new dihydropyridine calcium antagonist, were studied in comparison with those of nifedipine (NF) in isolated arteries of the dog (DG-AR) and isolated aorta (GP-AO), left and right atria (GP-LA, GP-RA) and ventricular papillary muscles (GP-PM) of the guinea pig. In DG-AR precontracted with high K+, LC and NF produced a concentration-dependent relaxation. The relaxant effect of LC was most potent in the basilar artery. The calcium antagonistic effects of LC was 8.7 and 2.1 times more potent than those of NF, in GP-AO and GP-LA, respectively. Thus, LC was about 4 times more selective towards vascular smooth muscles than NF. The negative chronotropic effects in GP-RA and the negative inotropic effect in GP-PM of NF were more pronounced than those of LC. NF was more potent in inhibiting the action potential of GP-PM than LC both in normal polarized and depolarized conditions. The effects of LC were long-lasting. These results suggest that LC is a potent, highly vascular-selective calcium antagonist with little cardiodepressant effects and as such may be suitable for the treatment of hypertension.
Kawada
T
T
Department of Pharmacology, Niigata University School of Medicine, Japan.
Sun
H T
HT
Nakazawa
M
M
Imai
S
S
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine; D009543:Nifedipine; D011188:Potassium