Analgesic Effects of 1st Generation Anti-histamines in Mice

• Takahashi Mebae

  Division of Molecular Regulation, Tohoku University Graduate School of Dentistry Division of Pediatric Dentistry, Tohoku University Graduate School of Dentistry

• Shima Kazuhiro

  Division of Molecular Regulation, Tohoku University Graduate School of Dentistry

• Tsuchiya Masahiro

  Tohoku Fukushi University

• Hagiwara Yoshihiro

  Department of Orthopedic Surgery, Tohoku University Graduate School of Medicine

• Mizoguchi Hirokazu

  Department of Physiology and Anatomy, Tohoku Pharmaceutical University

• Sakurada Shinobu

  Department of Physiology and Anatomy, Tohoku Pharmaceutical University

• Sugawara Shunji

  Division of Molecular Regulation, Tohoku University Graduate School of Dentistry

• Fujita Takuo

  Katsuragi Hospital and Calcium Research Institute

• Tadano Takeshi

  Department of Health Care Medical Research Venture Business Laboratory, Kanazawa University

• Watanabe Makoto

  Tohoku Fukushi University

• Fukumoto Satoshi

  Division of Pediatric Dentistry, Tohoku University Graduate School of Dentistry

• Endo Yasuo

  Division of Molecular Regulation, Tohoku University Graduate School of Dentistry

抄録

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 AHs 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 AHs are water soluble, we selected water-soluble NSAIDs. For direct comparison, drugs were intravenously injected 30 min before the above tests. Histamine-H1-receptor-deficient (H1R-KO) mice were used for evaluating H1-receptor-independent effects. The tested 1st AHs (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 AHs 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 AH, by itself or in combination with a cyclooxygenase-1 inhibitor, should undergo testing to evaluate its usefulness in analgesia.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

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

  公益社団法人 日本薬学会

キーワード

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

詳細情報

• CRID: 1390001204631773952
• NII論文ID: 130005141684
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b15-00755
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 027221208
• PubMed: 27040636
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027221208
• Web Site: https://www.jstage.jst.go.jp/article/bpb/39/4/39_b15-00755/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016362778
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可