( ±) : 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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We investigated effects of (±)-<I>cis</I>-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, [<SUP>3</SUP>H]quinuclidinyl benzilate (QNB) binding was saturable, and Scatchard plot analysis revealed a single population of binding sites with a K<SUB>d</SUB> of 22 pM and a maximal binding capacity of 60 fmol/mg protein. The competitive inhibition curve of the [<SUP>3</SUP>H]QNB binding by SNI-2011 was obtained, and its dissociation constant value calculated from IC<SUB>50</SUB> 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.


  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 78(3), 373-380, 1998-11-01

    The Japanese Pharmacological Society

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Cited by:  12


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