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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1989-11-1
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pubmed:abstractText |
The enantiomers of 5,6,7,8-tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten-8-++ +ylamine (3) have been synthesized and evaluated for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor activity by use of behavioral and biochemical tests in rats. In addition, the ability of the compounds to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The absolute configuration of the enantiomers of 3 was determined indirectly by X-ray diffraction of (+)-(8R,alpha R)-5,6,7,8-tetrahydro-1-methoxy-N-(alpha-phenethyl)-9H- benzocyclohepten-8-ylamine hydrochloride (9.HCl), a resolved synthetic precursor. The stereoselectivity of the interaction of 3 with 5-HT1A receptors was more pronounced than that of 8-hydroxy-2-(dipropylamino)tetralin (1; 8-OH-DPAT); only (R)-3 displayed 5-HT activity. However, (R)-3 was of lower potency than any of the enantiomers of 1. The enantiomer (S)-3, which was found to be inactive as a 5-HT-receptor agonist, appeared to be a weakly potent DA-receptor agonist whereas (R)-3 seemed to be devoid of dopaminergic activity. The conformational preferences of 3 were studied by use of NMR spectroscopy and molecular mechanics calculations. Preferred conformations of (R)-3 are similar in shape to those of the stereoselective 5-HT1A-receptor agonist (2R,3S)-8-hydroxy-3-methyl-2-(dipropylamino)tetralin.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/6,7,8,9-tetrahydro-1-hydroxy-N,N-dip...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzocycloheptenes,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Reserpine,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2311-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:2795604-Animals,
pubmed-meshheading:2795604-Benzocycloheptenes,
pubmed-meshheading:2795604-Brain,
pubmed-meshheading:2795604-Dopamine,
pubmed-meshheading:2795604-Male,
pubmed-meshheading:2795604-Models, Molecular,
pubmed-meshheading:2795604-Molecular Conformation,
pubmed-meshheading:2795604-Molecular Structure,
pubmed-meshheading:2795604-Motor Activity,
pubmed-meshheading:2795604-Rats,
pubmed-meshheading:2795604-Rats, Inbred Strains,
pubmed-meshheading:2795604-Receptors, Serotonin,
pubmed-meshheading:2795604-Reserpine,
pubmed-meshheading:2795604-Serotonin,
pubmed-meshheading:2795604-Serotonin Antagonists,
pubmed-meshheading:2795604-Stereoisomerism,
pubmed-meshheading:2795604-Structure-Activity Relationship,
pubmed-meshheading:2795604-X-Ray Diffraction
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pubmed:year |
1989
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pubmed:articleTitle |
(R)- and (S)-5,6,7,8-tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten- 8-ylamine. Stereoselective interactions with 5-HT1A receptors in the brain.
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pubmed:affiliation |
Department of Organic Pharmaceutical Chemistry, University of Uppsala, Sweden.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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