(±)-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

The Japanese Journal of Pharmacology

Toshie Tomizuka¹  Nobuo Ogane¹  Yuzo Nakagawa-Yagi¹  Hirohiko Arisawa¹  Yasunari Saito¹  Yoshinori Iga¹  Hiroaki Masunaga¹  Nobuo Miyata¹  Hiroshi Yasuda¹ 

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

关键词: SNI-2011;    Muscarinic agonist;    Sjögren’s syndrome;    Salivary gland;    Lacrimal gland;   

DOI  :  10.1254/jjp.78.373

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(27)Cited-By(27)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.

【 授权许可】

Unknown