Structure-related blockage of calcium channels by vasodilator alkamides in mice mesenteric artery

The development of new calcium channel blockers is still relevant for the understanding of their physiological role and pharmacological and therapeutic purposes. For this task, natural products represent a relevant source of new drugs. The present work investigated the mechanism and the structural relationship of the vasodilator effect of riparins I, II and III in mouse small mesenteric artery. Riparins I, II and III induced an endothelium-independent and concentration-dependent vasodilator effect in mesenteric arteries. Riparins II and III were more potent than riparin I, suggesting a structural relationship of the effect of these drugs. All riparins inhibited the contractile effect of KCl, similarly to nifedipine. However, the inhibitory profile was different for the contractile responses to phenylephrine and caffeine, passing from similar to nifedipine with riparin I, for similar to SKF-96365 with riparin III. A comparable effect was observed for the increase in the intracellular calcium concentration induced by caffeine and phenylephrine. These results suggest that the higher hydroxylation provides the alkamides the ability to inhibit non-selective cation channels in addition to the inhibition of L-type calcium channels in mouse mesenteric arteries. These observations may give support to the development of new selective inhibitors of non-selective cation channels using alkamides as leading compounds.

Figure optionsDownload high-quality image (175 K)Download as PowerPoint slide