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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
22
|
| pubmed:dateCreated |
1998-11-23
|
| pubmed:abstractText |
Muscarinic agonists were tested in two models indicative of clinical antipsychotic activity: conditioned avoidance responding (CAR) in rats and inhibition of apomorphine-induced climbing in mice. The standard muscarinic agonists oxotremorine and pilocarpine were both active in these tests but showed little separation between efficacy and cholinergic side effects. Structure-activity relationships of the alkylthio-1,2,5-thiadiazole azacyclic type muscarinic partial agonists are shown, revealing the exo-6-(3-propyl/butylthio-1,2, 5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane analogues (4a,b and 9a, b) to be the most potent antipsychotic agents with large separation between efficacy and cholinergic side effects. The lack of enantiomeric selectivity suggests the pharmacophoric elements are in the mirror plane of the compounds. A model explaining the potency differences of closely related compounds is offered. The data suggest that muscarinic agonists act as functional dopamine antagonists and that they could become a novel treatment of psychotic patients.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0022-2623
|
| pubmed:author |
pubmed-author:BymasterF PFP,
pubmed-author:CalligaroD ODO,
pubmed-author:DeLappN WNW,
pubmed-author:Fink-JensenAA,
pubmed-author:JeppesenLL,
pubmed-author:OlesenP HPH,
pubmed-author:RasmussenTT,
pubmed-author:RimvallKK,
pubmed-author:SauerbergPP,
pubmed-author:ShannonH EHE,
pubmed-author:SheardownM JMJ,
pubmed-author:SwedbergM DMD,
pubmed-author:ThøgersenHH,
pubmed-author:ThomsenCC,
pubmed-author:WareJ RJR
|
| pubmed:issnType |
Print
|
| pubmed:day |
22
|
| pubmed:volume |
41
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
4378-84
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9784113-Animals,
pubmed-meshheading:9784113-Antipsychotic Agents,
pubmed-meshheading:9784113-Avoidance Learning,
pubmed-meshheading:9784113-Brain,
pubmed-meshheading:9784113-Dopamine Antagonists,
pubmed-meshheading:9784113-Drug Evaluation, Preclinical,
pubmed-meshheading:9784113-Injections, Subcutaneous,
pubmed-meshheading:9784113-Male,
pubmed-meshheading:9784113-Mice,
pubmed-meshheading:9784113-Models, Molecular,
pubmed-meshheading:9784113-Molecular Conformation,
pubmed-meshheading:9784113-Motor Activity,
pubmed-meshheading:9784113-Muscarinic Agonists,
pubmed-meshheading:9784113-Rats,
pubmed-meshheading:9784113-Rats, Sprague-Dawley,
pubmed-meshheading:9784113-Salivation,
pubmed-meshheading:9784113-Stereoisomerism,
pubmed-meshheading:9784113-Structure-Activity Relationship,
pubmed-meshheading:9784113-Thiadiazoles,
pubmed-meshheading:9784113-Tremor
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Muscarinic agonists with antipsychotic-like activity: structure-activity relationships of 1,2,5-thiadiazole analogues with functional dopamine antagonist activity.
|
| pubmed:affiliation |
Health Care Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760 Mâlov, Denmark, and Neuroscience Research, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA. psa@novo.dk
|
| pubmed:publicationType |
Journal Article,
In Vitro
|