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.
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.
Iwabuchi
Y
Y
Department of Dental Pharmacology, School of Dentistry at Niigata, Nippon Dental University, Japan.
Masuhara
T
T
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology*; D018674:Adrenergic Antagonists; D000818:Animals; D018680:Cholinergic Antagonists; D008297:Male; D010862:Pilocarpine / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000502:physiology; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism*; D012472:Salivation / Q000187:drug effects*; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D013876:Thiophenes
D018674:Adrenergic Antagonists; D018680:Cholinergic Antagonists; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D013876:Thiophenes; D010862:Pilocarpine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; C059240:cevimeline