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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
1994-2-4
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pubmed:abstractText |
A series of 2-(dipropylamino)tetralin derivatives in which the C8 substituent is varied has been prepared and evaluated pharmacologically to explore the importance of the C8 substituent in the interaction of 2-aminotetralin-based ligands with serotonin (5-HT1A) receptors. Enantiopure derivatives were prepared by facile palladium-catalyzed reactions of the triflates of the enantiomers of 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT, 1). The affinity of the compounds for the 5-HT1A receptors was evaluated by competition experiments with [3H]-8-OH-DPAT in rat hippocampal and cortical tissue. In addition, the compounds were evaluated for central 5-HT and dopamine receptor stimulating activity in vivo by use of biochemical and behavioral assays in rats. With the exception of the carboxy-substituted derivative which is devoid of 5-HT1A receptor affinity, the compounds have moderate to high affinities (K(i) values range from 0.7 to 130 nM) for 5-HT1A receptors. Surprisingly, several of the derivatives do not produce any apparent effects in vivo although they have fairly high 5-HT1A receptor affinities. However, the methoxycarbonyl- and acetyl-substituted derivatives are potent 5-HT1A receptor agonists in vivo and exhibit in vitro affinities in the same range as the enantiomers of 1.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4221-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7506312-5-Hydroxytryptophan,
pubmed-meshheading:7506312-8-Hydroxy-2-(di-n-propylamino)tetralin,
pubmed-meshheading:7506312-Animals,
pubmed-meshheading:7506312-Binding, Competitive,
pubmed-meshheading:7506312-Body Temperature,
pubmed-meshheading:7506312-Brain,
pubmed-meshheading:7506312-Cerebral Cortex,
pubmed-meshheading:7506312-Chemistry, Physical,
pubmed-meshheading:7506312-Dihydroxyphenylalanine,
pubmed-meshheading:7506312-Dopamine,
pubmed-meshheading:7506312-Hippocampus,
pubmed-meshheading:7506312-Hydroxyindoleacetic Acid,
pubmed-meshheading:7506312-Male,
pubmed-meshheading:7506312-Molecular Structure,
pubmed-meshheading:7506312-Motor Activity,
pubmed-meshheading:7506312-Physicochemical Phenomena,
pubmed-meshheading:7506312-Rats,
pubmed-meshheading:7506312-Rats, Sprague-Dawley,
pubmed-meshheading:7506312-Receptors, Serotonin,
pubmed-meshheading:7506312-Reserpine,
pubmed-meshheading:7506312-Serotonin,
pubmed-meshheading:7506312-Stereoisomerism
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pubmed:year |
1993
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pubmed:articleTitle |
Derivatives of 2-(dipropylamino)tetralin: effect of the C8-substituent on the interaction with 5-HT1A receptors.
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pubmed:affiliation |
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Centre, Uppsala University, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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