Linked Life Data

7862933

Source:http://linkedlifedata.com/resource/pubmed/id/7862933

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-3-23
pubmed:abstractText
The present experiments examined the behavioral and receptor binding characteristics of new 5-HT1A methoxy-chroman derivatives in procedures known to be sensitive to the activity of 5-HT1A compounds. Key peck responding of pigeons was maintained by a 30-response fixed-ratio schedule of food delivery. In studies involving punished responding, every 30th response during one keylight stimulus also produced shock ("conflict" procedure). In drug discrimination studies, pigeons were trained to discriminate injections of the 5-HT1A agonist 8-OH-DPAT (0.3 mg/kg) from saline. Three forms of the methoxy-chroman compounds were tested: the enantiomers (+)S 20499 (0.01-3.0 mg/kg) and (-) S 20500 (0.3-5.6 mg/kg), as well as the racemic mixture (+)S 20244 (0.03-5.6 mg/kg). (+)S 20499 was approximately 10-fold more potent than (-)S 20500 in producing maximal increases in punished responding. (+)S 20244 was comparable in potency to (-)S 20500 in producing maximal increases in punished responding, but increases also occurred at much lower doses with (+)S 20244 and the magnitude of the effect with (-)S 20500 was less than that of the two other compounds. While increases in punished responding were observed with all three drugs at doses that did not affect unpunished responding, the highest doses of all drugs decreased unpunished responding. All compounds substituted for 8-OH-DPAT in the drug discrimination procedure, suggestive of 5-HT1A agonist activity. (+)S 20499 was approximately 30-fold more potent than (-)S 20500 in substituting for 8-OH-DPAT and 3-fold more potent than the racemate. All three compounds bound with high affinity to pigeon cerebrum receptor sites labelled by [3H]8-OH-DPAT. As in behavioral studies, (+)S 20499 was approximately 10-fold more potent than (-)S 20500 in displacing [3H]8-OH-DPAT (IC50 = 2.79 versus 20.3 nM). These studies demonstrate that the enantiomers of this compound, as well as the racemic mixture, are effective 5-HT1A compounds and that (+)S 20499 in particular is likely to be a clinically effective anxiolytic and/or antidepressant.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0033-3158
pubmed:author
pubmed:issnType
Print
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
73-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Anticonflict and discriminative stimulus effects in the pigeon of a new methoxy-chroman 5-HT1A agonist, (+)S 20244 and its enantiomers (+)S 20499 and (-)S 20500.
pubmed:affiliation
Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
pubmed:publicationType
Journal Article