In vivo binding of [125I]NH2-carfentanil to mu opioid receptors in mouse brain.
A functionalized derivative of the mu opioid agonist carfentanil was synthesized (NH2-carfentanil) and showed high specific activity when radiolabeled with iodine. [127I]NH2-carfentanil displayed high affinity and pronounced mu-binding selectivity with a delta/mu selectivity ratio of over 1200. The ability of [125I]NH2-carfentanil to interact in vivo with opioid receptors was determined in mouse brain using ex vivo binding techniques. Twenty minutes after intraperitoneal injection, 0.1% of the [125I]NH2-carfentanil injected into the mouse was present in the brain. [125I]NH2-carfentanil specific binding was inhibited by co-injection of naloxone or morphine while naltrindole, a delta-selective antagonist, was unable to displace the bound radioligand. Autoradiographic experiments revealed a heterogeneous distribution of [125I]NH2-carfentanil specific binding sites, maximal binding occurred in areas with high densities of mu receptors. Peripherally administered iodo-NH2-carfentanil selectively labelled central mu opioid receptors in mouse indicating great potential for single photon emission computed tomography studies.
Tafani
J A
JA
Service de Biophysique et de Médecine Nucléaire, CHU Purpan, Toulouse, France.
Francés
B
B
Coulais
Y
Y
Méjean-Galzi
A
A
Goeldner
M
M
Hirth
C
C
Guiraud
R
R
Zajac
J M
JM
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007457:Iodine Radioisotopes; D016015:Logistic Models; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D007457:Iodine Radioisotopes; D009292:Narcotic Antagonists; D009294:Narcotics; D017450:Receptors, Opioid, mu; C107950:iodoaminocarfentanil; D009270:Naloxone; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole; D005283:Fentanyl