Pharmacology of secoverine, a new spasmolytic agent with specific antimuscarinic properties. Part 1: Antimuscarinic and spasmolytic effects.
1-Cyclohexyl-4-[ethyl(p-methoxy-alpha-methylphenethyl)amino]-1-butanone hydrochloride (secoverine hydrochloride) is a neurotropic spasmolytic agent with specific antimuscarinic properties. On the basis of the results obtained, the possibility exists that secoverine acts only a sub-group of muscarinic receptors. 1. In in vitro experiments the competitive antagonism of secoverine against muscarinomimetics was demonstrated on guinea pig ileum, rat jejunum and calif trachea smooth muscle. On the basis of the mean difference of the pA2 values and in accordance with the relative activity as determined by 4-point assays, it may be concluded that secoverine is about 0.6 times as active as atropine. 2. In in vivo experiments the antimuscarinic activity of secoverine on ileum of guinea pig, rat and dog proved to be 0.6 times of atropine, by both parenteral and intraduodenal routes of administration. It was shown that the action of secoverine was reversible, of quick onset and of long duration. 3. By contrast, secoverine had only marginal effects on the sphincter and ciliary muscle of the eye, almost no effect on cholinergically-induced salivation and lacrimation, gastric acid production, urinary bladder function, gastric emptying or normal peristalsis. 4. The central anticholinergic activity was more in accordance with the activity found in the spasmolytic tests. 5. Apart from the neurotropic action, secoverine has also a good musculotropic activity as was found in in vivo and in vitro experiments. The activity varied from 3.3--13.3 times that of papaverine in the different organs investigated. The musculotropic activity is not caused by a specific, verapamil-like, calcium antagonism. 6. Secoverine has no nicotinolytic or antihistaminic activity, a moderate antisterotonic activity, an inhibiting effect on the noradrenaline uptake mechanism of the vas deferens and a marked local anaesthetic activity.
D000779:Anesthetics, Local; D000818:Animals; D002415:Cats; D002606:Charcoal / Q000378:metabolism; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects
D000779:Anesthetics, Local; D010276:Parasympatholytics; D010627:Phenethylamines; D002606:Charcoal; C028187:secoverine