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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Role of the histamine system in nefopam-induced antinociception in mice.

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.[1]


  1. Role of the histamine system in nefopam-induced antinociception in mice. Girard, P., Pansart, Y., Coppé, M.C., Verniers, D., Gillardin, J.M. Eur. J. Pharmacol. (2004) [Pubmed]
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