Selective abolition of Ca-dependent responses of smooth and cardiac muscles by flunarizine.

The inhibitory effect of flunarizine on the Ca-dependent responses was compared with that of verapamil in isolated smooth and cardiac muscles. Flunarizine at a small dose shifted to the right the dose-response curve for Ca2+ of the phasic contraction due to electric stimuli in rabbit basilar strips, while in a large dose, flunarizine reduced the maximum tension and slope of the dose-response curve. The high K+-induced vasoconstriction of the rabbit basilar artery was inhibited by flunarizine. However, the action of flunarizine was about 30 times slower than findings with verapamil. The spontaneous activity of the rat portal vein was less susceptible to flunarizine, whereas that of rat uterus was completely inhibited by flunarizine. Flunarizine possessed moderate negative chronotropic and inotropic actions on the right atria and papillary muscles of the rabbit. Our experiments indicate that flunarizine is selective in antagonizing Ca-dependent contraction of the rabbit basilar artery, probably by blockade of the transmembrane Ca. It is also possible that the slow onset of action and nonsurmountable antagonism produced by flunarizine is due to other pharmacological interventions such as delayed effect of metabolites, stabilizing action or tight binding on the cell membrane of vascular smooth muscles.