Agonist-antagonist properties of fluorescent opioid probes in the guinea-pig myenteric plexus-longitudinal muscle preparation.

The opioid activity of a series of fluorescent derivatives of oxymorphone, naloxone and naltrexone, were characterized on the electrically stimulated guinea-pig myenteric plexus-longitudinal muscle preparation. In all compounds the fluorescent moiety, fluorescein or tetramethylrhodamine B, is attached to the C-6 carbon of the morphinan. Mu-receptor affinity was well retained and there was a good correlation between capacity to displace [3H]-dihydromorphine from binding sites in rat brain membranes and apparent receptor affinity in the myenteric plexus measured as antagonism of normorphine effects. Fluorescein conjugated oxymorphone showed mainly agonist activity. Certain derivatives of the antagonists naloxone and naltrexone showed partial agonism. One compound, 1-(N)-fluoresceinyl naloxone thiosemicarbazone, was an antagonist.