In view of recent pharmacological studies suggesting the existence of δ-κ opioid receptor heterodimers/oligomers in the spinal cord, we have synthesized and evaluated (intrathecally in mice) a series of bivalent ligands (KDN series) containing κ and δ antagonist pharmacophores. Pharmacological and binding data have provided evidence for the bridging of spinal δ-κ receptor heterodimers by KDN-21 and for their identification as δ1 and κ2. The selectivity profile of KDN-21 and the apparent absence of coupled δ 1-κ2 phenotypes in the brain suggest a new approach for targeting receptors.
|Original language||English (US)|
|Number of pages||4|
|Journal||Journal of medicinal chemistry|
|State||Published - Jun 3 2004|