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

作者：Vujovic Katarina R Savic^*; Vuckovic Sonja; Srebro Dragana; Ivanovic Milovan; Dosen Micovic Ljiljana; Vucetic Cedomir; Dzoljic Eleonora; Prostran Milica

来源：Archives of Pharmacal Research, 2013, 36(4): 501-508.

DOI：10.1007/s12272-013-0072-z

• Fentanyl
• Morphine
• Derivatives
• Temperature
• Antinociception
• Rats

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 mu-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)a parts per thousand yenT(0.11)a parts per thousand yenB(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)> F(1)> C(0.46)a parts per thousand yenT(0.11)a parts per thousand yenB(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-alpha,alpha,17-trimethyl-, (5 alpha,7 alpha) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)> O(5)a parts per thousand yenT(2.6)> M(1), and similar to this, the relative order of hyperthermic potency was: E(37)> O(3)a parts per thousand yenT(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.

• 出版日期2013-4