DIMERS OF 5HT(1) LIGANDS PREFERENTIALLY BIND TO 5HT(1B 1D) RECEPTOR SUBTYPES/

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) r eceptors. Binding experiments show that all these dimers have better a ffinities at 5HT(1B/1D) receptors than their corresponding monomeric l igands. Studies of inhibition of the forskolin-stimulated c-AMP format ion mediated by the human 5HT(1B) receptor show that hetero-bivalent l igands [combining an agonist (5HT) with an antagonist (I-NP)] behave a s partial agonists while the intrinsic activity of bivalent antagonist s (combining two I-NP residues) was found to be spacer dependent. Surp risingly enough, the dimer of 8-OH-DPAT 6 binds to 5HT(1A), 5HT(1B) an d 5HT(1D) receptors with similar high affinity, (C) 1998 Elsevier Scie nce Ltd. All rights reserved.