Resultant pharmacological actions of verapamil: quantification of competitive 5-hydroxytryptamine antagonism in combination with calcium antagonism.

According to previous reports, the effect of verapamil on 5-hydroxytryptamine (5-HT) responses in the rabbit aorta is likely to represent a resultant of 5-HT2-receptor antagonism and Ca++-channel blockade. In practice, verapamil produced rightward displacement and depression of 5-HT-concentration-effect curves in this tissue. Under these conditions, verapamil's competitive property may not be justifiably quantified by analyzing curve displacements. In order to detect and quantify this property, a recently developed concentration-ratios method was applied. This method depends on the effect of the test substance, verapamil here, on the expression of competition by a standard antagonist, spiperone in this study. Analysis of the concentration-ratios produced by spiperone in the presence of verapamil permitted receptor competition by verapamil to be detected. Quantification of this property indicated a pKB of 5.73. This estimate of affinity did not account for the total rightward displacement of 5-HT-concentration-effect curves that verapamil produced, indicating, presumably, that concomitant Ca++-antagonism contributed to these displacements. Also, this estimate of verapamil's 5-HT2-receptor affinity is lower than that derived elsewhere from an analysis of the overall antagonistic effect of verapamil on 5-HT responses in the rabbit aorta. These results illustrate the potentially general utility of the concentration-ratios methods in elucidating resultant pharmacological actions.