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

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Galzi JL, Mejean A, Ilien B, Mollereau C, Meunier JC, Goeldner M, Hirth C

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

J Med Chem. 1990 Sep;33(9):2456-64.

PubMed ID

2167979 [ View in PubMed

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Abstract

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

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Carfentanil	Kappa-type opioid receptor	Ki (nM)	92	N/A	N/A	Details