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 beta 1-,beta 2-, and alpha-adrenergic receptors, inhibition of phosphodiesterase activity, and antagonism of calcium accumulation. Isoproterenol and perhexiline only exhibited binding to beta-adrenergic sites. Ergocryptine, tolazoline, and amotriphene only bound to alpha-adrenergic receptors. Leniquinsin, papaverine, proquazone, dioxyline, hoquizil, quazodine, and theophylline were active only as phosphodiesterase inhibitors. Isoxsuprine, nylidrin, and bencyclane bound to alpha- and beta-receptors. Pentoxifylline bound to beta 1-sites and inhibited phosphodiesterase. Cyclandelate bound to beta 2-sites and blocked calcium accumulation. Cinnarizine and flunarizine antagonized calcium accumulation and bound to alpha-sites. Prazosin bound to alpha-sites and inhibited phosphodiesterase. Ethaverine and dipyridamole were inhibitors of phosphodiesterase and calcium accumulation. Nafronyl bound to beta 2- and alpha-sites and antagonized calcium accumulation. Mebeverine bound to beta 2- and alpha-receptors and inhibited phosphodiesterase activity and calcium accumulation. Verapamil bound to alpha-sites, and blocked phosphodiesterase and calcium accumulation. Quinazosin bound to beta 2- and alpha-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.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D002118:Calcium