(+/-)-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
Y. Iga et al., (+/-)-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, JPN J PHARM, 78(3), 1998, pp. 373-380
We investigated effects of (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-qui
nuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride),
a rigid analogue of acetylcholine, on saliva and tear secretions in rats a
nd mice to evaluate its therapeutical efficacy for xerostomia and xerophtha
lmia 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 r
ats and mice, two strains of autoimmune disease mice and X-irradiated saliv
a secretion defective rats. The salivation elicited by SNI-2011 was complet
ely inhibited by atropine. A similar atropine-sensitive response was observ
ed in tear secretion. In rat submandibular/sublingual gland membranes, [H-3
]quinuclidinyl benzilate (QNB) binding was saturable, and Scatchard plot an
alysis revealed a single population of binding sites with a K-d Of 22 PM an
d a maximal binding capacity of 60 fmol/mg protein. The competitive inhibit
ion curve of the [H-3]QNB binding by SNI-2011 was obtained, and its dissoci
ation constant value calculated from IC50 was 1-2 mu M. These results sugge
st that SNI-2011 increases saliva and tear secretions through a direct stim
ulation to muscarinic receptors in salivary and lacrimal glands, and they s
uggest that SNI-2011 should be beneficial to patients with Sjogren's syndro
me and X-ray exposure in the head and neck.