General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). II. Actions on the cardiovascular system, intestinal transit and central nervous system.

The effects of 1-(2-methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-piperazine-dihydrochloride (zipeprol, 3024 CERM, Respilene), a new nonopiate antitussive agent, have been studied on the cardiovascular system, intestinal function and the central nervous system. Most of these studies were performed comparatively with reference antitussives, particularly codeine, whose activites in these fields are the basis of its undesirable side effects. In the dog, zipeprol showed no hypotensive or cardiac-depressant activity. It did not alter pulmonary arterial pressure. An important antiarrhythmic action was apparent in studies on rhythm disturbances induced by ouabain and coronary ligation. Intestinal function, measured by the recording of peristaltic movements in the dog and the speed of intestinal transit in the rat, was not modified by the product. Zipeprol showed no characteristic action on the central nervous system. Analgesic activity was seen only at doses just below toxic levels. Finally in the rat and the mouse, no evidence of physical dependence was seen after prolonged treatment. This together with the absence of chemical similarity to the morphinics, leads to exclude the possibility of zipeprol treatment leading to addiction. The results of these studies allow zipeprol to be clearly distinguished from the opiate antitussives.