Effects of New Synthetic Acyl Aniline and Acyl Aminopyridine Derivatives on Calcium Entry in Rat Vas Deferens

Abstract

A number of the synthetic acyl aniline derivatives and acyl aminopyridine derivatives were shown to reduce the contraction of rabbit isolated duodenum and rat isolated aorta. Previous studies have shown that the effects of acy1-4-aniline derivatives (CU 18-07, CU 18-09) and acyl-4-aminopyridine derivative (CU 18-12) on the contraction of rat isolated aorta were attributed to their effects on disrupting Ca²⁺ entry. This study was to further investigate the potential effects of these compounds on the contraction and their pharmacological mode of actions. The contractile responses were measured isometrically in in vitro model of rat isolated vas deferens under various conditions. Our results showed that these three compounds were able to suppress the contraction evoked by noradrenaline (NA), KCl and BaCl₂ in Ca²⁺-containing solution, but not in Ca²⁺-free solution. In addition, they also suppressed CaCl₂-induced contraction in high K⁺ depolarizing solution. Of the three compounds, CU 18-09 was the most potent inhibitor. Our results suggested that all of the synthetic CU compounds in this study exerted their pharmacological actions on the contraction of rat isolated vas deferens possibly by blockade of the Ca²⁺ entry through the voltage-operated Ca²⁺ channels. In addition, the modification of molecular structure at para-position on the phenyl ring affected the inhibitory potency of these compounds on smooth muscle contraction.