Effect of spasmolytics on cathartic activity of pilocarpine, 5-HT and prostaglandin E₂ in mice

Abstract

Effects of autonomic, anti-histaminic, anti-5HT drugs, papaverine and morphine on cathartic activity of spasmogens such as pilocarpine, 5-HT and prostaglandin E₂ (PGE₂) were tested by giving these drugs to mice subcutaneously. Mice used were male dd strain weighing 20±2 g and the cathartic effect was evaluated by the all or none method. The cathartic effect by pilocarpine was inhibited markedly by anti-cholinergic drugs such as atropine and diphenhydramine, but not by hexamethonium and methysergide. Therefore, the action of pilocarpine was found to be direct on the acetylcholine receptors. The cathartic effect by 5-HT was inhibited significantly by hexamethonium and methysergide. Atropine inhibited the cathartic effect of 5-HT, but the inhibitory activity was lower by about one hundredth than that on pilocarpine-induced diarrhea. It is suggested that 5-HT has dual sites of actions and there are less cholinergic and specific serotonergic actions. The cathartic effect by PGE₂ was inhibited by anticholinergic, anti-5HT and ganglion blocking agents. PGE₂ appears to possess the same mode of action as both pilocarpine and 5-HT. Papaverine inhibited little the cathartic effect of all three spasmogens, while morphine had a potent and nonspecific inhibitory effect on the cathartic action of all three spasmogens.