Effects of beta-funaltrexamine on radiolabeled opioid binding.
beta-Funaltrexamine (beta-FNA) potently competed with the binding of a series of radiolabeled opiates and opioid peptides in standard binding assays with IC50 values under 10 nM. In addition, higher concentrations of beta-FNA produced an irreversible inhibition of binding which was relatively selective for mu receptors; delta binding was not affected much. The production of irreversible inhibition of [3H]dihydromorphine binding required concentrations of beta-FNA over 10-fold higher than beta-FNA concentrations needed in standard competition studies. Both mu 1 and mu 2 sites were irreversibly inhibited by beta-FNA, but mu 1 sites were more sensitive. The reversible and irreversible inhibition in these in vitro binding assays by beta-FNA were quite similar to naloxonazine. However, the activity of beta-FNA in the guinea-pig ileum suggests that it may not distinguish between mu 1 and mu 2 receptors as effectively as naloxonazine in bioassays and in vivo.
Recht
L D
LD
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Pasternak
G W
GW
D000818:Animals; D001667:Binding, Competitive; D004090:Dihydromorphine / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004743:Enkephalin, Leucine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C024524:beta-funaltrexamine; D009020:Morphine; D004090:Dihydromorphine