Analgesic Effects of 1st Generation Anti-histamines in Mice.

Abstract

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.

• Authors: Mebae Takahashi, Kazuhiro Shima, Masahiro Tsuchiya, Yoshihiro Hagiwara, Hirokazu Mizoguchi, Shinobu Sakurada, Shunji Sugawara, Takuo Fujita, Takeshi Tadano, Makoto Watanabe, Satoshi Fukumoto, Yasuo Endo
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 39 Issue 4 Pg. 620-4 ( 2016) ISSN: 1347-5215 [Electronic] Japan
• PMID: 27040636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic Antagonists
• Analgesics
• Anti-Inflammatory Agents, Non-Steroidal
• Cholinergic Antagonists
• Histamine Antagonists
• Serotonin Antagonists
• Acetic Acid

Topics

• Acetic Acid
• Adrenergic Antagonists (therapeutic use)
• Analgesics (therapeutic use)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Cholinergic Antagonists (therapeutic use)
• Female
• Histamine Antagonists (therapeutic use)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Knockout
• Pain (chemically induced, drug therapy)
• Serotonin Antagonists (therapeutic use)