A bivalent ligand (KDN-21) reveals spinal δ and κ opioid receptors are organized as heterodimers that give rise to δ1 and δ2 phenotypes. Selective targeting of δ-κ heterodimers

Rashmi G. Bhushan, Shiv K. Sharma, Zhihua Xie, David J. Daniels, Philip S Portoghese

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Abstract

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 12 phenotypes in the brain suggest a new approach for targeting receptors.

Original languageEnglish (US)
Pages (from-to)2969-2972
Number of pages4
JournalJournal of Medicinal Chemistry
Volume47
Issue number12
DOIs
StatePublished - Jun 3 2004

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Opioid Receptors
Pharmacology
Ligands
Phenotype
Spinal Cord
Brain
KDN 21

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A bivalent ligand (KDN-21) reveals spinal δ and κ opioid receptors are organized as heterodimers that give rise to δ1 and δ2 phenotypes. Selective targeting of δ-κ heterodimers. / Bhushan, Rashmi G.; Sharma, Shiv K.; Xie, Zhihua; Daniels, David J.; Portoghese, Philip S.

In: Journal of Medicinal Chemistry, Vol. 47, No. 12, 03.06.2004, p. 2969-2972.

Research output: Contribution to journalArticle

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