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] 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.
Masunaga
H
H
Life Science Research Institute, Snow Brand Milk Products Co., Ltd., Shimotsuga-gun, Tochigi, Japan.
Ogawa
H
H
Uematsu
Y
Y
Tomizuka
T
T
Yasuda
H
H
Takeshita
Y
Y
D000818:Animals; D004285:Dogs; D005260:Female; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012472:Salivation / Q000187:drug effects*; D012636:Secretory Rate / Q000187:drug effects; D013876:Thiophenes; D013997:Time Factors
D018721:Muscarinic Agonists; D011812:Quinuclidines; D013876:Thiophenes; D010862:Pilocarpine; C059240:cevimeline