LONG-LASTING SALIVATION INDUCED BY A NOVEL MUSCARINIC RECEPTOR AGONIST SNI-2011 IN RATS AND DOGS

The sialogogic effect of SNI-2011, a novel muscarinic receptor agonist , (+/-)-cis-2-methylspilo [1,3-oxathiolane-5,3'-quinuclidine] hydrochl oride, hemihydrate, was compared with that of pilocarpine hydrochlorid e in a dose range in which the two muscarinic agonists exhibited appro ximately similar efficacy in eliciting salivation. Pilocarpine (0.66-2 .0 mg/kg, i.d.) induced a marked but short-lasting salivation in rats, whereas the salivation induced by SNI-2011 (20-60 mg/kg i.d.) lasted 1.4- to 1.8-fold longer. In dogs, the sialogogic effect of SNI-2011(1- 3 mg/kg, i.v.) also lasted about 2-fold longer than that of pilocarpin e (0.1-0.3 mg/kg, i.v.). The plasma SNI-2011 level that caused salivat ion at a rate of 0.4 ml/min was about 100 ng/ml and higher rates of sa livation (over 0.4 ml/min) induced by 1 mg/kg SNI-2011 lasted for abou t 90 min in dogs. The plasma pilocarpine level that caused salivation at a rate of 0.4 ml/min was about 25 ng/ml and the higher rate of sali vation (over 0.4 ml/min) induced by 0.1 mg/kg pilocarpine lasted only for 20 min in dogs. Effective plasma levels of SNI-2011 persisted long er than those of pilocarpine. These results indicate that SNI-2011 may be useful in the treatment of xerostomia because of its long-lasting sialogogic action. (C) 1997 Elsevier Science B.V.