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ID: ALA1131387

Journal: Bioorg Med Chem Lett

Title: Dimers of 5HT1 ligands preferentially bind to 5HT1B/1D receptor subtypes.

Authors: Perez M, Jorand-Lebrun C, Pauwels PJ, Pallard I, Halazy S.

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.

CiteXplore: 9871775

DOI: 10.1016/s0960-894x(98)00222-4