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

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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.

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Acknowledgments

This work was supported by Ministry of Education, Science and Technological Development of Serbia (Grant No. 175023). The author would like to convey thanks to Alkaloid (Skopje, Macedonia) and University of Debrecen, Hungary, who gifted us some of the compounds tested.

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Authors and Affiliations

  1. Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Katarina R. Savić Vujović, Sonja Vučković, Dragana Srebro & Milica Prostran

  2. Faculty of Chemistry, University of Belgrade, Belgrade, Serbia

    Milovan Ivanović & Ljiljana Došen-Mićović

  3. Institute for Orthopaedic Surgery and Traumatology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Čedomir Vučetić

  4. Neurology Clinic, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Eleonora Džoljić

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  1. Katarina R. Savić Vujović
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  2. Sonja Vučković
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  3. Dragana Srebro
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  4. Milovan Ivanović
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  7. Eleonora Džoljić
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  8. Milica Prostran
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Correspondence to Katarina R. Savić Vujović.

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Savić Vujović, K.R., Vučković, S., Srebro, D. et al. A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats. Arch. Pharm. Res. 36, 501–508 (2013). https://doi.org/10.1007/s12272-013-0072-z

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  • DOI: https://doi.org/10.1007/s12272-013-0072-z

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