(±)-cis-2-Methylspiro[1,3-oxathiolane-5,3′-quinuclidine] Hydrochloride, Hemihydrate(SNI-2011, Cevimeline Hydrochloride) Induces Saliva and Tear Secretions in Rats and Mice:The Role of Muscarinic Acetylcholine Receptors

• Iga Yoshinori

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

• Arisawa Hirohiko

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

• Ogane Nobuo

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

• Saito Yasunari

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

• Tomizuka Toshie

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

• Nakagawa-Yagi Yuzo

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

• Masunaga Hiroaki

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

• Yasuda Hiroshi

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

• Miyata Nobuo

  Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.

書誌事項

タイトル別名

• (.+-.)-cis-2-Methylspiro (1,3-oxathiolane-5,3'-quinuclidine) Hydrochloride, Hemihydrate (SNI-2011, Cevimeline Hydrochloride) Induces Saliva and Tear Secretions in Rats and Mice: The Role of Muscarinic Acetylcholine Receptors.
• プラスマイナス cis 2 Methylspiro 1 3 oxathiola
• (±)-cis-2-Methylspiro[1,3-oxathiolane-5,3-quinuclidine] Hydrochloride, Hemihydrate (SNI-2011, Cevimeline Hydrochloride) Induces Saliva and Tear Secretions in Rats and Mice: The Role of Muscarinic Acetylcholine Receptors

抄録

We investigated effects of (±)-cis-2-methylspiro[1, 3-oxathiolane-5, 3′-quinuclidine] hydrochlo- ride, hemihydrate (SNI-2011, cevimeline hydrochloride), a rigid analogue of acetylcholine, on saliva and tear secretions in rats and mice to evaluate its therapeutical efficacy for xerostomia and xerophthalmia in patients with Sjögren’s syndrome and X-ray exposure in the head and neck. Intraduodenal administrations of SNI-2011 increased saliva secretion in a dose-dependent manner at doses ranging from 3 to 30 mg/kg in normal rats and mice, two strains of autoimmune disease mice and X-irradiated saliva secretion defective rats. The salivation elicited by SNI-2011 was completely inhibited by atropine. A similar atropine-sensitive response was observed in tear secretion. In rat submandibular/sublingual gland membranes, [³H]quinuclidinyl benzilate (QNB) binding was saturable, and Scatchard plot analysis revealed a single population of binding sites with a K_d of 22 pM and a maximal binding capacity of 60 fmol/mg protein. The competitive inhibition curve of the [³H]QNB binding by SNI-2011 was obtained, and its dissociation constant value calculated from IC₅₀ was 1 - 2 μM. These results suggest that SNI-2011 increases saliva and tear secretions through a direct stimulation to muscarinic receptors in salivary and lacrimal glands, and they suggest that SNI-2011 should be beneficial to patients with Sjögren’s syndrome and X-ray exposure in the head and neck.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 78 (3), 373-380, 1998

  公益社団法人 日本薬理学会

キーワード

• SNI-2011
• Muscarinic agonist
• Sjögren’s syndrome
• Salivary gland
• Lacrimal gland

詳細情報

• CRID: 1390001204286086144
• NII論文ID: 10008681425
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.78.373
• COI: 1:CAS:528:DyaK1cXnslyktbw%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL書誌ID: 4610827
• PubMed: 9869272
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4610827
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819310376?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819310376?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/78/3/78_3_373/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1999089001
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可