Heterogeneity of Biochemical Actions Among Vasodilators

Thirty-four vasodilators were screened in several in vitro biochemical assays related to smooth muscle excitation-contraction coupling, binding to β1-, β2-, and α-adrenergic receptors, inhibition of phosphodiesterase activity, and antagonism of calcium accumulation. Isoproterenol and perhexiline only exhibited binding to β-adrenergic sites. Ergocryptine, tolazoline, and amotriphene only bound to α-adrenergic receptors. Leniquinsin, papaverine, proquazone, dioxyline, hoquizil, quazodine, and theophylline were active only as phosphodiesterase inhibitors. Isoxsuprine, nylidrin, and bencyclane bound to α- and β-receptors. Pentoxifylline bound to β1-sites and inhibited phosphodiesterase. Cyclandelate bound to β2-sites and blocked calcium accumulation. Cinnarizine and flunarizine antagonized calcium accumulation and bound to α-sites. Prazosin bound to α-sites and inhibited phosphodiesterase. Ethaverine and dipyridamole were inhibitors of phosphodiesterase and calcium accumulation. Nafronyl bound to β2- and α-sites and antagonized calcium accumulation. Mebeverine bound to β2- and α-receptors and inhibited phosphodiesterase activity and calcium accumulation. Verapamil bound to α-sites, and blocked phosphodiesterase and calcium accumulation. Quinazosin bound to β2- and α-receptors and antagonized both phosphodiesterase activity and calcium accumulation. Vasodilators that were inactive in all assays included niacin, nicotinyl alcohol, inositol nicotinate, amyl nitrite, sodium nitroprusside, diazoxide, hydralazine, and protoveratrine. Vasodilators should not be considered as a single drug class since they act on various mechanisms related to coupling of neuronal excitation to muscular contractility.