Analgesic Effects of 1st Generation Anti-histamines in Mice

作者：Takahashi Mebae; Shima Kazuhiro; Tsuchiya Masahiro; Hagiwara Yoshihiro; Mizoguchi Hirokazu; Sakurada Shinobu; Sugawara Shunji; Fujita Takuo; Tadano Takeshi; Watanabe Makoto; Fukumoto Satoshi; Endo Yasuo^*

来源：Biological & Pharmaceutical Bulletin, 2016, 39(4): 620-624.

DOI：10.1248/bpb.b15-00755

• anti-histamine
• analgesic effect
• non-steroidal anti-inflammatory drug
• cyproheptadine
• pain
• histamine-H1-receptor

Pain is sensed, transmitted, and modified by a variety of mediators and receptors. Histamine is a well-known mediator of pain. In addition to their anti-histaminic effects, the classical, or 1st generation, anti-histamines (1st AHs) possess, to various degrees, anti-muscarinic, anti-serotonergic, anti-adrenergic, and other pharmacologic effects. Although there have been attempts to use 1st Ails as analgesics and/or analgesic adjuvants, the advent of non-steroidal anti-inflammatory drugs (NSAIDs) discouraged such trials. We previously reported that in patients with temporomandibular disorders, osteoporosis, and/or osteoarthritis, the analgesic effects of certain 1st AHs (chlorpheniramine and diphenhydramine) are superior to those of the NSAIDs flurbiprofen and indomethacin. Here, we compared analgesic effects among 1st AHs and NSAIDs against responses shown by mice to intraperitoneally injected 0.7% acetic acid. Since 1st Ails are water soluble, we selected water-soluble NSAIDs. For direct comparison, drugs were intravenously injected 30min before the above tests. Histamine-H1-receptor-deficient (H1R-KO) mice were used for evaluating 111-receptor-independent effects. The tested 1st Ails (especially cyproheptadine) displayed or tended to display analgesic effects comparable to those of NSAIDs in normal and H1R-KO mice. Our data suggest that the anti-serotonergic and/or anti-adrenergic effects of 1st Ails make important contributions to their analgesic effects. Moreover, combination of a 1st AH with an NSAID (cyclooxygenase-1 inhibitor) produced remarkably potent analgesic effects. We propose that a 1st Ail, by itself or in combination with a cyclooxygenase-1 inhibitor, should undergo testing to evaluate its usefulness in analgesia.

• 出版日期2016-4