Synthesis and pharmacological characterization of fluorescent opioid receptor probes

A series of five fluorescent opioid receptor probes was synthesized by coupling naloxone, oxymorphone or naltrexone with fluorescein or tetramethylrhodamine B. The series was characterized for capacity to displace (3)H-dihydromorphine from rat brain opioid receptors. All compounds showed receptor binding, and 1-(N)-fluoresceinyl naltrexone thiosemicarbazone displayed the highest mu-receptor affinity with a Ki value of 3 nM. l-(N)-fluoresceinyl naloxone thiosemicarbazone was a morphine antagonist in vivo, approximately 6 % as potent as naloxone and naloxonazine in the mouse hot-plate test.