A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats

Arch Pharm Res. 2013 Apr;36(4):501-8. doi: 10.1007/s12272-013-0072-z. Epub 2013 Feb 26.

Abstract

In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of μ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (±)-cis-3-methyl fentanyl (CM), (±)-cis-3-carbomethoxy fentanyl (C), (±)trans-3-carbomethoxy fentanyl (T) and (±)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27)>F(1)>C(0.35)≥T(0.11)≥B(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46)≥T(0.11)≥B(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-α,α,17-trimethyl-, (5α,7α) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)>O(5)≥T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3)≥T(2.3)>M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6-11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Body Temperature / drug effects*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fentanyl / analogs & derivatives
  • Fentanyl / pharmacology*
  • Fever / chemically induced*
  • Fever / physiopathology
  • Male
  • Molecular Structure
  • Morphine Derivatives / pharmacology*
  • Pain / etiology
  • Pain / physiopathology
  • Pain / prevention & control*
  • Pain Measurement
  • Pain Perception / drug effects
  • Pain Threshold / drug effects
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Structure-Activity Relationship
  • Time Factors

Substances

  • Analgesics, Opioid
  • Morphine Derivatives
  • Fentanyl