Potentiated hypnotic action with a combination of fentanyl, a calcium channel blocker and an alpha 2-agonist in rats.

An investigation was made of the hypnotic-anaesthetic effects in rats of subcutaneous coadministration of fentanyl (25-100 micrograms.kg-1), clonidine (100-300 micrograms.kg-1) and verapamil (1-5 mg.kg-1). Hypnotic-anaesthetic efficacy was assessed via loss of the righting reflex. In the doses used, none of the three drugs alone was associated with appreciable hypnotic-anaesthetic effects. Coadministration of fentanyl and clonidine resulted in a dose-related enhancement of the anaesthetic potency, without change in the duration of hypnotic action. Verapamil coadministration failed to increase the anaesthetic efficacy of binary combinations of fentanyl and clonidine, but a marked prolongation of the duration of hypnotic action was observed (P less than 0.001). These results suggest the existence of unreported interactions between these three drugs in the production of hypnotic-anaesthetic action in rats.