Sialogogic activities of SNI-2011 compared with those of pilocarpine and McN-A-343 in rat salivary glands: identification of a potential therapeutic agent for treatment of Sjörgen's syndrome

Gen Pharmacol. 1994 Jan;25(1):123-9. doi: 10.1016/0306-3623(94)90021-3.

Abstract

1. We examined the sialogogic activities in rat major salivary glands of SNI-2011, in comparison with those of pilocarpine and McN-A-343, and we characterized the subtypes of muscarine receptors that are involved in the sialogogic responses to SNI-2011 and McN-A-343. 2. SNI-2011 at doses ranging from 1 to 10 mg/kg (i.v.) increased the secretion of saliva in a dose-dependent manner. The dose-response curves for SNI-2011 were approximately parallel to curves for pilocarpine but the potency of SNI-2011 was about 25-fold lower than that of pilocarpine. 3. The total volume of saliva secreted in response to McN-A-343 was very much less than that secreted in response to SNI-2011. 4. The salivation induced by SNI-2011 and by McN-A-343 was inhibited by various antagonists with the following rank order of potency: 4-DAMP >> pirenzepine >> AF-DX 116. 5. Our results suggest that the sialogogic effects of SNI-2011 and McN-A-343 are mediated by direct stimulation of M3 receptors in salivary glands and that SNI-2011 may prove useful in the management of xerostomia in patients with Sjögren's syndrome.

Publication types

  • Comparative Study

MeSH terms

  • (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / pharmacology*
  • Adrenergic Antagonists
  • Animals
  • Cholinergic Antagonists
  • Male
  • Pilocarpine / pharmacology*
  • Quinuclidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / classification
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology
  • Salivary Glands / drug effects*
  • Salivary Glands / metabolism*
  • Salivation / drug effects*
  • Sjogren's Syndrome / drug therapy*
  • Sjogren's Syndrome / physiopathology
  • Thiophenes*

Substances

  • Adrenergic Antagonists
  • Cholinergic Antagonists
  • Quinuclidines
  • Receptors, Muscarinic
  • Thiophenes
  • Pilocarpine
  • (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
  • cevimeline