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.

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Abstract-Effect of AF102B (cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinucli dine) on experimental amnesia was examined using a passive avoidance task in rodents. The amnesia was produced by anti-cholinergic agents, AF64A (intra cerebroventricularly) and scopolamine (subcutaneously).AF102B ameliorated the memory deficits in AF64A-treated rats at 0.1-1 mg/kg, i.p. and at 1-5 mg/kg p.o. and in scopolamine-treated mice at 1-10 mg/kg, i.p. These results suggest that AF1 02B may compensate for central cholinergic defects and could be developed as a possible therapeutic drug for senile dementia of the Alzheimer type.