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)3T(0.11)3B (0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46)3T(0.11)3B(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)3T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3)3T(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.