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Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic
Gianfranco Balboni1, Severo Salvadori, Ewa D Marczak
1Department of Toxicology, University of Cagliari, Via Ospedale 72, I-09124 Cagliari, Italy. gbalboni@unica.it
Abstract:
Bifunctional ligands containing an ester linkage between morphine and the δ-selective pharmacophore Dmt-Tic were synthesized, and their binding affinity and functional bioactivity at the micro, δ and κ opioid receptors determined. Bifunctional ligands containing or not a spacer of β-alanine between the two pharmacophores lose the micro agonism deriving from morphine becoming partial micro agonists 4 or micro antagonists 5. Partial κ agonism is evidenced only for compound 4. Finally, both compounds showed potent δ antagonism.
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