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Nefopam and ketoprofen synergy in rodent models of antinociception.
Eur J Pharmacol. 2008 Apr 28; 584(2-3):263-71.EJ

Abstract

Combinations of analgesics with different mechanisms of action offer the possibility of efficient analgesia with a decrease in side effects as a result of reduced dosages of one or both compounds. Based on a clinical observation of synergism between nefopam, a centrally acting non-opioid that inhibits monoamines reuptake, and ketoprofen, a non-steroidal anti-inflammatory drug, the objective of this study was to further explore this antinociceptive synergy in four distinct animal models of pain (both drugs were administered subcutaneously). Strong antinociceptive properties were observed in the mouse writhing abdominal test with ED50 values of 2.56+/-0.38 and 1.41+/-0.41 mg/kg for nefopam and ketoprofen, respectively. In the inflammatory phase of the mouse formalin test, both compounds significantly inhibited the licking time of the injected hind-paw with ED50 of 4.32+/-0.17 mg/kg for nefopam and 49.56+/-15.81 mg/kg for ketoprofen. Isobolographic analysis revealed that this drug combination is synergistic in the formalin test and additive in the writhing test. In rat carrageenan-induced tactile allodynia, single administration of nefopam or ketoprofen only partially reduced allodynia. Combination of low analgesic doses of nefopam (10 or 30 mg/kg) with low analgesic doses of ketoprofen (30 or 100 mg/kg) significantly reduced or reversed allodynia, with a more pronounced anti-allodynic effect and a longer duration efficacy. In a rat model of postoperative thermal hyperalgesia induced by incision, co-administration of nefopam at a low analgesic dose (10 mg/kg) with ketoprofen at non-analgesic doses (30 or 100 mg/kg) showed the appearance of a strong anti-hyperalgesic effect, maintained during at least 3 h. In conclusion, co-administration of nefopam with ketoprofen is synergistic, and should allow either to increase their analgesic efficacy and/or to reduce their side effects.

Authors+Show Affiliations

Biocodex, Service de Pharmacologie, Zac de Mercières 60200 Compiègne, France. p.girard@biocodex.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18316069

Citation

Girard, Philippe, et al. "Nefopam and Ketoprofen Synergy in Rodent Models of Antinociception." European Journal of Pharmacology, vol. 584, no. 2-3, 2008, pp. 263-71.
Girard P, Verniers D, Coppé MC, et al. Nefopam and ketoprofen synergy in rodent models of antinociception. Eur J Pharmacol. 2008;584(2-3):263-71.
Girard, P., Verniers, D., Coppé, M. C., Pansart, Y., & Gillardin, J. M. (2008). Nefopam and ketoprofen synergy in rodent models of antinociception. European Journal of Pharmacology, 584(2-3), 263-71. https://doi.org/10.1016/j.ejphar.2008.02.012
Girard P, et al. Nefopam and Ketoprofen Synergy in Rodent Models of Antinociception. Eur J Pharmacol. 2008 Apr 28;584(2-3):263-71. PubMed PMID: 18316069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nefopam and ketoprofen synergy in rodent models of antinociception. AU - Girard,Philippe, AU - Verniers,Danielle, AU - Coppé,Marie-Claude, AU - Pansart,Yannick, AU - Gillardin,Jean-Marie, Y1 - 2008/02/14/ PY - 2007/10/03/received PY - 2008/01/18/revised PY - 2008/02/06/accepted PY - 2008/3/5/pubmed PY - 2008/7/2/medline PY - 2008/3/5/entrez SP - 263 EP - 71 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 584 IS - 2-3 N2 - Combinations of analgesics with different mechanisms of action offer the possibility of efficient analgesia with a decrease in side effects as a result of reduced dosages of one or both compounds. Based on a clinical observation of synergism between nefopam, a centrally acting non-opioid that inhibits monoamines reuptake, and ketoprofen, a non-steroidal anti-inflammatory drug, the objective of this study was to further explore this antinociceptive synergy in four distinct animal models of pain (both drugs were administered subcutaneously). Strong antinociceptive properties were observed in the mouse writhing abdominal test with ED50 values of 2.56+/-0.38 and 1.41+/-0.41 mg/kg for nefopam and ketoprofen, respectively. In the inflammatory phase of the mouse formalin test, both compounds significantly inhibited the licking time of the injected hind-paw with ED50 of 4.32+/-0.17 mg/kg for nefopam and 49.56+/-15.81 mg/kg for ketoprofen. Isobolographic analysis revealed that this drug combination is synergistic in the formalin test and additive in the writhing test. In rat carrageenan-induced tactile allodynia, single administration of nefopam or ketoprofen only partially reduced allodynia. Combination of low analgesic doses of nefopam (10 or 30 mg/kg) with low analgesic doses of ketoprofen (30 or 100 mg/kg) significantly reduced or reversed allodynia, with a more pronounced anti-allodynic effect and a longer duration efficacy. In a rat model of postoperative thermal hyperalgesia induced by incision, co-administration of nefopam at a low analgesic dose (10 mg/kg) with ketoprofen at non-analgesic doses (30 or 100 mg/kg) showed the appearance of a strong anti-hyperalgesic effect, maintained during at least 3 h. In conclusion, co-administration of nefopam with ketoprofen is synergistic, and should allow either to increase their analgesic efficacy and/or to reduce their side effects. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18316069/Nefopam_and_ketoprofen_synergy_in_rodent_models_of_antinociception_ DB - PRIME DP - Unbound Medicine ER -