H. Masunaga et al., LONG-LASTING SALIVATION INDUCED BY A NOVEL MUSCARINIC RECEPTOR AGONIST SNI-2011 IN RATS AND DOGS, European journal of pharmacology, 339(1), 1997, pp. 1-9
The sialogogic effect of SNI-2011, a novel muscarinic receptor agonist
, (+/-)-cis-2-methylspilo [1,3-oxathiolane-5,3'-quinuclidine] hydrochl
oride, hemihydrate, was compared with that of pilocarpine hydrochlorid
e in a dose range in which the two muscarinic agonists exhibited appro
ximately 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 pilocarpin
e (0.1-0.3 mg/kg, i.v.). The plasma SNI-2011 level that caused salivat
ion at a rate of 0.4 ml/min was about 100 ng/ml and higher rates of sa
livation (over 0.4 ml/min) induced by 1 mg/kg SNI-2011 lasted for abou
t 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 sali
vation (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 long
er 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. (C) 1997 Elsevier Science B.V.