Enhancement of fentanyl analgesia by clonidine plus verapamil in rats

G. Horvath, G. Benedek, M. Szikszay

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An investigation was made of the analgesic effects of the subcutaneous coadministration of fentanyl, an opioid μ-agonist (15 μg/kg), clonidine, an α2-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 antinociception. These results suggest the existence of hitherto unreported interactions between drugs involved in the production of analgesia.

Original languageEnglish
Pages (from-to)284-288
Number of pages5
JournalAnesthesia and analgesia
Issue number3
Publication statusPublished - Jan 1 1990



  • analgesics, sympathetic nervous system, pharmacology
  • fentanyl, clonidine, verapamil, analgesia
  • interactions (drug)
  • pharmacology

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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