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Enhancement of Fentanyl Analgesia by Clonidine Plus Verapamil in Rats

Received from the Division of Health Visitors and the Department of Physiology, Albert Szent-Gyürgyi Medical University, Szeged, Hungary.

Abstract

An investigation was made of the analgesic effects of the subcutaneous coad ministration of fentanyl, an opioid µ- agonist (15 µg/kg), clonidine, an ₂-agonist (100 µg/kg), and verapamil, a calcium channel blocker (10 mg/kg) in rats. Nociceptive sensitivity was assessed with hot-plate and tail-flick techniques. None of the three drugs alone was associated with appreciable analgesic effects in the doses used. The simultaneous administration of the three drugs resulted in marked analgesia superior to that of all binary combinations of these drugs. Two-way analysis of variance showed statistically significant differences in hot-plate and tail-flick latencies after drug treatments (P < 0.001). The significant differences in the area under the time-response curve values (P < 0.001) might indicate not only an increased analgesic effect, but also a prolongation of anti- nociception. These results suggest the existence of hitherto unreported interactions between drugs involved in the production of analgesia.

Key Words: INTERACTIONS (DRUG)—fentanyl, clonidine, verapamil • ANALGESIA—fentanyl, clonidine, verapamil • ANALGESICS, FENTANYL • SYMPATHETIC NERVOUS SYSTEM, PHARMACOLOGY—clonidine • PHARMACOLOGY, VERAPAMIL

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