Linked Life Data

9152397

Source:http://linkedlifedata.com/resource/pubmed/id/9152397

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-6-12
pubmed:abstractText
Butylthio[2.2.2] ((+)-(S)-3-(4-(Butylthio)-1,2,5-thiadiazol-3-yl)-1-azabicyclo[2.2. 2] octane) is an agonist/antagonist at muscarinic receptors. The analgesic potential of butylthio[2.2.2] was assessed in the mouse by use of the grid-shock, tail-flick, hotplate and writhing tests. The ED50 values ranged from 0.19 to 1.47 mg/kg and 1.51 to 12.23 mg/kg 30 min after s.c. and p.o. administration, respectively, yielding p.o./s.c. ratios ranging from 7 to 27. The ED50 values for salivation and tremor were > 30 and 12.31 mg/kg s.c., and > 60 and > 60 mg/kg p.o., yielding therapeutic windows > 130 and 54, and, > 40 and > 40, after s.c. and p.o. administration, respectively. Motor impairment or lethality were only seen at doses 116 and 254 times higher than the antinociceptive doses. Butylthio[2.2.2] was equieffective to, and 3- to 24-fold more potent than morphine. The duration of action was similar to that of morphine. The dose-response curve was shifted dose dependently to the right by the muscarinic antagonist scopolamine but not by the opioid antagonist naltrexone. The antinociceptive effect of butylthio[2.2.2] was reversed by the centrally acting muscarinic antagonist scopolamine but not by the peripherally acting muscarinic antagonist methscopolamine. After 6.5 days repeated dosing in mice, morphine produced marked tolerance, whereas butylthio[2.2.2] produced minimal, if any, tolerance. In the rat grid-shock test, ED50 values of 0.26 mg/kg s.c. and 25.28 mg/kg p.o. were obtained. These data show that butylthio[2.2.2] is a potent and efficacious antinociceptive with a very favorable therapeutic window after s.c. and p.o. administration in mice, and with good efficacy in rats.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
876-83
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Butylthio[2.2.2] (NNC 11-1053/LY297802): an orally active muscarinic agonist analgesic.
pubmed:affiliation
Novo Nordisk, Health Care Discovery, Malov, Denmark.
pubmed:publicationType
Journal Article