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Role of the histamine system in nefopam-induced antinociception in mice.
Eur J Pharmacol. 2004 Oct 25; 503(1-3):63-9.EJ

Abstract

The present study explored the role of the histaminergic system in nefopam analgesia based on the structural relationship between nefopam and diphenhydramine. In vitro binding assays revealed that nefopam possesses moderate affinity for histamine H1 and H2 receptor subtypes, with IC50 of 0.8 and 6.9 microM, respectively, but no affinity for histamine H(3) receptor subtype until 100 microM. Subcutaneous nefopam administration dose-dependently inhibited pain in acetic acid-induced writhing (1-30 mg/kg) and formalin (1-10 mg/kg) tests in the mouse. Pretreatment with the histamine-depleting agent alpha-fluoromethylhistidine (alpha-FMH, 50 mg/kg), the histamine H1 receptor antagonist pyrilamine (3 or 10 mg/kg), or the histamine H2 receptor antagonists cimetidine (100 mg/kg) and zolantidine (10 or 30 mg/kg) did not significantly modify nefopam antinociception in both tests. The histamine H3 receptor agonist R(-)alpha-methylhistamine (RAMH, 10 mg/kg) did not significantly modify the nefopam analgesic activity in the writhing test. At 25 mg/kg, RAMH inhibited nefopam antinociception at 3 mg/kg, but not at 10 mg/kg in the formalin test. However, pretreatment with the histamine H3 receptor antagonist thioperamide (25 mg/kg) inhibited nefopam antinociception in the writhing test, but not in the formalin test. In conclusion, nefopam analgesic activity is not mediated by histamine H1 or H2 receptors, but can be slightly modulated by histamine H3 receptors in mouse pain tests.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15496297

Citation

Girard, Philippe, et al. "Role of the Histamine System in Nefopam-induced Antinociception in Mice." European Journal of Pharmacology, vol. 503, no. 1-3, 2004, pp. 63-9.
Girard P, Pansart Y, Coppé MC, et al. Role of the histamine system in nefopam-induced antinociception in mice. Eur J Pharmacol. 2004;503(1-3):63-9.
Girard, P., Pansart, Y., Coppé, M. C., Verniers, D., & Gillardin, J. M. (2004). Role of the histamine system in nefopam-induced antinociception in mice. European Journal of Pharmacology, 503(1-3), 63-9.
Girard P, et al. Role of the Histamine System in Nefopam-induced Antinociception in Mice. Eur J Pharmacol. 2004 Oct 25;503(1-3):63-9. PubMed PMID: 15496297.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the histamine system in nefopam-induced antinociception in mice. AU - Girard,Philippe, AU - Pansart,Yannick, AU - Coppé,Marie-Claude, AU - Verniers,Danielle, AU - Gillardin,Jean-Marie, PY - 2004/05/07/received PY - 2004/09/08/revised PY - 2004/09/14/accepted PY - 2004/10/22/pubmed PY - 2005/4/26/medline PY - 2004/10/22/entrez SP - 63 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 503 IS - 1-3 N2 - The present study explored the role of the histaminergic system in nefopam analgesia based on the structural relationship between nefopam and diphenhydramine. In vitro binding assays revealed that nefopam possesses moderate affinity for histamine H1 and H2 receptor subtypes, with IC50 of 0.8 and 6.9 microM, respectively, but no affinity for histamine H(3) receptor subtype until 100 microM. Subcutaneous nefopam administration dose-dependently inhibited pain in acetic acid-induced writhing (1-30 mg/kg) and formalin (1-10 mg/kg) tests in the mouse. Pretreatment with the histamine-depleting agent alpha-fluoromethylhistidine (alpha-FMH, 50 mg/kg), the histamine H1 receptor antagonist pyrilamine (3 or 10 mg/kg), or the histamine H2 receptor antagonists cimetidine (100 mg/kg) and zolantidine (10 or 30 mg/kg) did not significantly modify nefopam antinociception in both tests. The histamine H3 receptor agonist R(-)alpha-methylhistamine (RAMH, 10 mg/kg) did not significantly modify the nefopam analgesic activity in the writhing test. At 25 mg/kg, RAMH inhibited nefopam antinociception at 3 mg/kg, but not at 10 mg/kg in the formalin test. However, pretreatment with the histamine H3 receptor antagonist thioperamide (25 mg/kg) inhibited nefopam antinociception in the writhing test, but not in the formalin test. In conclusion, nefopam analgesic activity is not mediated by histamine H1 or H2 receptors, but can be slightly modulated by histamine H3 receptors in mouse pain tests. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15496297/Role_of_the_histamine_system_in_nefopam_induced_antinociception_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(04)01090-8 DB - PRIME DP - Unbound Medicine ER -