Photoactivatable opiate derivatives as irreversible probes of the mu-opioid receptor.

摘要: The synthesis of aryldiazonium and arylazido derivatives carfentanil, etonitazene, naltrexone a triazaspirodecane derivative is described. chemical stability the spectral characteristics these compounds were verified, their binding affinity constants for different opioid receptor classes determined, in absence light, from competition experiments. With exception naltrexyl derivatives, which remained nonselective, all tested displayed pronounced mu-binding selectivity with mu/delta mu/kappa ratios ranging 12 to 1000. After irradiation, only probes led an irreversible mu-binding-site inactivation. This inactivation fulfilled criteria photoaffinity labeling such as protection against by other opiate ligands effect scavengers on extent Most photoactivatable formed long-lasting reversible complexes sites: efficient dissociation procedure was thus required discriminate between pseudoirreversible covalent complexes. marked differences efficacy salts corresponding are discussed.