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

被引：27

作者：

Perez, M

Jorand-Lebrun, C

Pauwels, PJ

Pallard, I

Halazy, S

机构：

[1] Ctr Rech Pierre Fabre, Div Med Chem, F-81106 Castres, France

[2] Ctr Rech Pierre Fabre, Dept Cellular & Mol Biol, F-81106 Castres, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(98)00222-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New dimers of known 5HT(1) ligands (5HT, 1-NP or 8-OH-DPAT) have, been prepared and evaluated at human cloned 5HT(1B), 5HT(1D) and 5HT(1A) receptors. Binding experiments show that all these dimers have better affinities at 5HT(1B/1D) receptors than their corresponding monomeric ligands. Studies of inhibition of the forskolin-stimulated c-AMP formation mediated by the human 5HT(1B) receptor show that hetero-bivalent ligands [combining an agonist (5HT) with an antagonist (I-NP)] behave as partial agonists while the intrinsic activity of bivalent antagonists (combining two I-NP residues) was found to be spacer dependent. Surprisingly enough, the dimer of 8-OH-DPAT 6 binds to 5HT(1A), 5HT(1B) and 5HT(1D) receptors with similar high affinity, (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：1407 / 1412

页数：6

共 20 条

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[2]

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