Salivary secretion and histopathological effects after single administration of the muscarinic agonist SNI-2011 in MRL/lpr mice.

The salivary secretion and the histopathological effects after administration of a single dose of cis-2-methylspiro (1,3-oxathiolane-5,3') quinuclidine hydrochloride hemihydrate (SNI-2011) were monitored in adult, male and female MRL/lpr mice, C57BL/6J mice and ICR mice. SNI-2011 (1-10 mg/kg, i.p.), dose-dependently increased the secretion of saliva in MRL/lpr mice. The flow rate decreased gradually over the course of 60 min. The total volume of saliva, secreted in response to SNI-2011, was significantly higher in male than in female MRL/lpr mice, but there was no significant difference in this parameter between male and female C57BL/6J and ICR mice. Degeneration, apparent as atrophy and necrosis of serous cells in MRL/lpr mice, was reversed by treatment with SNI-2011 (3 and 6 mg/kg). These results suggest that SNI-2011 could be useful in the treatment of xerostomia in patients with Sjögren's syndrome.