(+/-)-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, H Arisawa, N Ogane, Y Saito, T Tomizuka, Y Nakagawa-Yagi, H Masunaga, H Yasuda, N Miyata

Jpn J Pharmacol. 1998 Nov;78(3):373-80.

PMID: 9869272

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP153504702	Cevimeline hydrochloride hemihydrate		153504-70-2	Price