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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.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Masunaga H,Ogawa H,Uematsu Y,Tomizuka T,Yasuda H,Takeshita Y

doi

10.1016/s0014-2999(97)01338-1

subject

Has Abstract

pub_date

1997-11-19 00:00:00

pages

1-9

issue

1

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(97)01338-1

journal_volume

339

pub_type

杂志文章

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