Pharmacology of secoverine, a new spasmolytic agent with specific antimuscarinic properties. Part 2: General pharmacological properties.
The general pharmacological properties of 1-cyclohexyl-4-[ethyl(p-methoxy-alpha-methylphenethyl)amino]-1-butanone hydrochloride (secoverine hydrochloride), a neurotropic spasmolytic agent with specific antimuscarinic properties, are described. 1. No effects on blood pressure were seen in dogs with doses up to 3 mg/kg .i.v. In hypertensive rats no blood pressure lowering effect was seen after oral doses of 25 and 100 mg/kg. In cats a marginal increase of the blood pressure was observed with i.v. doses up to 3 mg/kg, in pentobarbital-anaesthetized animals. This effect was not present in the chloralose-anaesthetized animal. The sinus carotis occlusion pressor reflex was increased at doses of 0.1 and 0.3 mg/kg but was decreased after an i.v. dose of 3 mg/kg. At a dose of 1 mg/kg i.v. a small decrease in heart contractility was seen. At relative high concentrations, secoverine showed in vitro a non-specific negative inotropic effect on the isolated atrium and rat ventricle strip. 2. No serious effects on the ECG were found in dogs with i.v. doses up to 10 mg/kg. In rabbits at 1 mg/kg i.v. atrioventricular dissociation was seen. In cats irregularly, anaesthetic dependent ventricular ectopics were observed. 3. With 10 mg/kg i.v. doses in rabbits some increase in respiration volume occurred, due to an increase in respiratory frequency and tidal volume. 4. Secoverine had no central depressant effects. In high doses central stimulating effects probably related to the antimuscarinic activity were found. 5. Secoverine did not cause ulceration of the stomach wall of the rat during acute or prolonged oral administration of high doses. A potentiation of ulceration was observed in Shay rats; however, the ulceration in rats caused by acetyl salicylic acid and by reserpine was antagonized by the compound. 6. No effects were seen on blood glucose levels, blood coagulation, platelet aggregation, detoxification mechanisms and diuresis, neither were analgetic or antiinflammatory effects observed.
D000700:Analgesics; D000818:Animals; D000893:Anti-Inflammatory Agents; D001831:Body Temperature / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects; D004285:Dogs; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology* / Q000633:toxicity; D010627:Phenethylamines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D012119:Respiration / Q000187:drug effects
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010276:Parasympatholytics; D010627:Phenethylamines; C028187:secoverine