EPA-0510 - A comparison of the effect of morphine and fentanyl derivatives on the antinociception and body temperature in rats

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 in male Wistar rats (200–250 g). The distal 5 cm of the tail was immersed in a warm water bath (55 + 0.5°C) and the time for tail-withdrawal was measured as a response latency. The body temperature was measured by insertion of a thermometer probe 5 cm into the colon of unrestrained rats. 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) 3 T(0.11) 3 B (0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46) 3 T(0.11) 3 B(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-Ethenomorphinan-7-methanol, 4,5-epoxy-6- fluoro-3-hydroxy-a, a,17-trimethyl-, (5a,7a) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)>O(5) 3 T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3) 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 to 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.