Enhancement of fentanyl analgesia by clonidine plus verapamil in rats

Anesth Analg. 1990 Mar;70(3):284-8.


An investigation was made of the analgesic effects of the subcutaneous coadministration of fentanyl, an opioid mu-agonist (15 micrograms/kg), clonidine, an alpha 2-agonist (100 micrograms/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 less than 0.001). The significant differences in the area under the time-response curve values (P less than 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.

MeSH terms

  • Animals
  • Clonidine / pharmacokinetics
  • Clonidine / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Synergism
  • Fentanyl / pharmacokinetics
  • Fentanyl / pharmacology*
  • Injections, Subcutaneous
  • Male
  • Nociceptors / drug effects*
  • Rats
  • Rats, Inbred Strains
  • Verapamil / pharmacokinetics
  • Verapamil / pharmacology*


  • Drug Combinations
  • Verapamil
  • Clonidine
  • Fentanyl