Fluorescent probes for opioid receptors.
Naloxone, naltrexone and oxymorphone were labeled in position 6 with fluorescein by coupling their hydrazone analogs with fluorescein isothiocyanate. Naloxone was also coupled in a similar way with rhodamine-B. The compounds thus obtained were: "6-FN", [1-(N)-fluoresceinyl naloxone thiosemicarbazone]; "6-FNX", [1-(N)-fluoresceinyl naltrexone thiosemicarbazone]; "6-FO", [1-(N)-fluoresceinyl oxymorphone thiosemicarbazone]; "6-RN", [1-(N)-tetramethylrhodaminyl-B naloxone thiosemicarbazone]. These compounds were tested for opioid receptor binding in rat brain synaptosomal plasma membranes and for biological activity on the guinea pig ileum. All compounds retained activity, showing some changes in affinity and binding profile compared to their parent compounds. "6-FN", for example, showed decreased (approximately 10x) affinity compared to naloxone in opiate displacement analysis but retained potency in displacement of opioid peptides. Antagonist activity of "6-FN" in the guinea pig ileum bioassay was about ten-fold less than that of naloxone.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013574:Synaptosomes / Q000378:metabolism
D005456:Fluorescent Dyes; D009292:Narcotic Antagonists; D011957:Receptors, Opioid