Long-lasting salivation induced by a novel muscarinic receptor agonist SNI-2011 in rats and dogs

Eur J Pharmacol. 1997 Nov 19;339(1):1-9. doi: 10.1016/s0014-2999(97)01338-1.


The sialogogic effect of SNI-2011, a novel muscarinic receptor agonist, (+/-)-cis-2-methylspilo [1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, was compared with that of pilocarpine hydrochloride in a dose range in which the two muscarinic agonists exhibited approximately 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 pilocarpine (0.1-0.3 mg/kg, i.v.). The plasma SNI-2011 level that caused salivation at a rate of 0.4 ml/min was about 100 ng/ml and higher rates of salivation (over 0.4 ml/min) induced by 1 mg/kg SNI-2011 lasted for about 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 salivation (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 longer 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.

MeSH terms

  • Animals
  • Dogs
  • Female
  • Male
  • Muscarinic Agonists / pharmacology*
  • Pilocarpine / pharmacology
  • Quinuclidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Salivation / drug effects*
  • Secretory Rate / drug effects
  • Thiophenes*
  • Time Factors


  • Muscarinic Agonists
  • Quinuclidines
  • Thiophenes
  • Pilocarpine
  • cevimeline