Suppressive Effects of Glycyrrhetinic Acid Derivatives on Tachykinin Receptor Activation and Hyperalgesia

• Akasaka Yuko

  Research Laboratory, Minophagen Pharmaceutical Co., Ltd., Japan

• Sakai Atsushi

  Department of Pharmacology, Nippon Medical School, Japan

• Takasu Kumiko

  Department of Pharmacology, Nippon Medical School, Japan

• Tsukahara Michiko

  Research Laboratory, Minophagen Pharmaceutical Co., Ltd., Japan

• Hatta Akira

  Research Laboratory, Minophagen Pharmaceutical Co., Ltd., Japan

• Suzuki Hidenori

  Department of Pharmacology, Nippon Medical School, Japan

• Inoue Hideo

  Research Laboratory, Minophagen Pharmaceutical Co., Ltd., Japan

抄録

Glycyrrhetinic acid (GA), an aglycone of glycyrrhizin, isolated from the licorice root (Glycyrrhizia), and its semi-synthetic derivatives have a wide range of pharmacological effects. To investigate whether GA derivatives may be used as a new class of analgesics, we examined the effects of these compounds on human tachykinin receptors expressed in CHO-K1 cells. Among the GA derivatives examined, the disodium salt of olean-11,13(18)-dien-3β,30-O-dihemiphthalate inhibited the mobilization of [Ca²⁺]_i induced by substance P, neurokinin A, and neurokinin B in CHO-K1 cells expressing the human NK₁, NK₂, and NK₃ tachykinin receptors, respectively. In an inflammatory pain model, Compound 5 suppressed the capsaicin-induced flinching behavior in a dose-dependent manner. Compound 5 was also effective in suppressing pain-related behaviors in the late phase of the formalin test and reducing thermal hyperalgesia in the neuropathic pain state caused by sciatic nerve injury. Collectively, Compound 5 may be an analgesic candidate via tachykinin receptor antagonism.

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 117 (3), 180-188, 2011

  公益社団法人 日本薬理学会

キーワード

• glycyrrhetinic acid
• inflammatory pain
• neuropathic pain
• substance P
• tachykinin receptor

詳細情報

• CRID: 1390001205179234304
• NII論文ID: 10030453357
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.11116fp
• COI: 1:CAS:528:DC%2BC3MXhsFygs7rJ
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 023320129
• PubMed: 22032861
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023320129
• Web Site: https://search.jamas.or.jp/link/ui/2012214118
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
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