( ±) : 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
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概要
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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 Kd 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.
- 社団法人 日本薬理学会の論文
- 1998-11-01
著者
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YASUDA Hiroshi
Research Center for Radiation Protection, National Institute of Radiological Sciences
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MIYATA Nobuo
Research Institute of Life Science
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Miyata Nobuo
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Nakagawa-yagi Yuzo
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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IGA Yoshinori
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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ARISAWA Hirohiko
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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OGANE Nobuo
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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SAITO Yasunari
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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TOMIZUKA Toshie
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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MASUNAGA Hiroaki
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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Ogane Nobuo
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Iga Yoshinori
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Saito Yasunari
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Tomizuka Toshie
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Arisawa Hirohiko
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Masunaga H
Snow Brand Milk Products Co. Ltd. Tochigi Jpn
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Masunaga Hiroaki
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Yasuda Hiroshi
Research Center For Advanced Science And Technology University Of Tokyo
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Yasuda Hiroshi
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Yasuda Hiroshi
Research Center For Advanced Science And Technology The University Of Tokyo
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YASUDA Hiroshi
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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