title: In vivo binding of [125I]NH2-carfentanil to mu opioid receptors in mouse brain.
abstract: 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.
authors.affiliation: Service de Biophysique et de Médecine Nucléaire, CHU Purpan, Toulouse, France.
authors.forename: J A
authors.initials: JA
authors.lastname: Tafani
authors.forename: B
authors.initials: B
authors.lastname: Francés
authors.forename: Y
authors.initials: Y
authors.lastname: Coulais
authors.forename: A
authors.initials: A
authors.lastname: Méjean-Galzi
authors.forename: M
authors.initials: M
authors.lastname: Goeldner
authors.forename: C
authors.initials: C
authors.lastname: Hirth
authors.forename: R
authors.initials: R
authors.lastname: Guiraud
authors.forename: J M
authors.initials: JM
authors.lastname: Zajac
mesh_terms: 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*
chemical_list: D007457:Iodine Radioisotopes; D009292:Narcotic Antagonists; D009294:Narcotics; D017450:Receptors, Opioid, mu; C107950:iodoaminocarfentanil; D009270:Naloxone; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole; D005283:Fentanyl