(+/-)-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.
(+/-)-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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( /-)-cis-2-methylspiro[1,3-oxathiolane-5,3-quinuclidine] 盐酸盐，半水合物（SNI-2011，盐酸西维美林）诱导大鼠和小鼠唾液和泪液分泌：毒蕈碱乙酰胆碱的作用
DOI：
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
N. Miyata
中科院分区：
文献类型：
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作者：
Y. Iga;H. Arisawa;N. Ogane;Y. Saito;T. Tomizuka;Y. Nakagawa;H. Masunaga;H. Yasuda;N. Miyata
我们研究了 (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] 盐酸盐半水合物（SNI-2011，盐酸西维美林）（一种乙酰胆碱的刚性类似物）对大鼠和小鼠唾液和泪液分泌物的影响，以评估其对干燥综合征患者口干症和干眼症以及头部和颈部 X 射线暴露患者的治疗效果。脖子。在正常大鼠和小鼠、两种自身免疫性疾病小鼠和 X 射线照射唾液分泌缺陷大鼠中，十二指肠内给予 SNI-2011，剂量范围为 3 至 30 mg/kg，以剂量依赖性方式增加唾液分泌。 SNI-2011 引起的流涎被阿托品完全抑制。在泪液分泌中观察到类似的阿托品敏感反应。在大鼠下颌下/舌下腺膜中，[3H]苯苯甲酸奎宁环酯 (QNB) 结合是饱和的，Scatchard 图分析显示单一结合位点群，Kd 为 22 pM，最大结合能力为 60 fmol/mg 蛋白质。获得SNI-2011与[3H]QNB结合的竞争性抑制曲线，由IC50计算出其解离常数值为1-2μM。这些结果表明，SNI-2011 通过直接刺激唾液腺和泪腺中的毒蕈碱受体来增加唾液和泪液分泌，并且表明 SNI-2011 对患有干燥综合征和头颈部 X 射线暴露的患者有益。
We investigated effects of (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, 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 Sjogren'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 microM. 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.
MRL/l 小鼠干燥综合征样疾病的超微结构研究。
DOI：
10.1111/j.1600-0714.1988.tb01316.x
发表时间：
1988
期刊：
Journal of oral pathology
影响因子：
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作者：
Tanaka,A;O'Sullivan,FX;Koopman,WJ;Gay,S
通讯作者：
Gay,S
影响因子：
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作者：
HOFFMAN, RW;ALSPAUGH, MA;WALKER, SE
通讯作者：
WALKER, SE