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

Abstract

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.

• Authors: H Masunaga, H Ogawa, Y Uematsu, T Tomizuka, H Yasuda, Y Takeshita
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 339 Issue 1 Pg. 1-9 (Nov 19 1997) ISSN: 0014-2999 [Print] Netherlands
• PMID: 9450610 (Publication Type: Journal Article)

Chemical References

• Muscarinic Agonists
• Quinuclidines
• Thiophenes
• Pilocarpine
• cevimeline

Topics

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