Abstract
New dimers of known 5HT1 ligands (5HT, 1-NP or 8-OH-DPAT) have been prepared and evaluated at human cloned 5HT1B, 5HT1D and 5HT1A receptors. Binding experiments show that all these dimers have better affinities at 5HT1B/1D receptors than their corresponding monomeric ligands. Studies of inhibition of the forskolin-stimulated c-AMP formation mediated by the human 5HT1B receptor show that hetero-bivalent ligands [combining an agonist (5HT) with an antagonist (1-NP)] behave as partial agonists while the intrinsic activity of bivalent antagonists (combining two 1-NP residues) was found to be spacer dependent. Surprisingly enough, the dimer of 8-OH-DPAT 6 binds to 5HT1A, 5HT1B and 5HT1D receptors with similar high affinity.
MeSH terms
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8-Hydroxy-2-(di-n-propylamino)tetralin / analogs & derivatives
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8-Hydroxy-2-(di-n-propylamino)tetralin / chemistry
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8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
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Cyclic AMP / antagonists & inhibitors
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Humans
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Ligands
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Piperazines / chemistry
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Piperazines / metabolism
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Radioligand Assay
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Receptor, Serotonin, 5-HT1B
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Receptor, Serotonin, 5-HT1D
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Receptors, Serotonin / metabolism*
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Receptors, Serotonin, 5-HT1
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Recombinant Proteins / metabolism
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Serotonin / analogs & derivatives
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Serotonin / chemistry
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Serotonin / metabolism
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Serotonin Agents / chemical synthesis*
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Serotonin Agents / chemistry
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Serotonin Agents / metabolism
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Serotonin Antagonists / chemistry
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Serotonin Antagonists / metabolism
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Serotonin Receptor Agonists / chemistry
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Serotonin Receptor Agonists / metabolism
Substances
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HTR1B protein, human
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Ligands
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Piperazines
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Receptor, Serotonin, 5-HT1B
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Receptor, Serotonin, 5-HT1D
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT1
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Recombinant Proteins
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Serotonin Agents
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Serotonin
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1-(1-naphthyl)piperazine
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8-Hydroxy-2-(di-n-propylamino)tetralin
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Cyclic AMP