IN-VIVO BINDING OF [I-125] NH2-CARFENTANIL TO MU-OPIOID RECEPTORS IN MOUSE-BRAIN

A functionalized derivative of the mu opioid agonist carfentanil was s ynthesized (NH2-carfentanil) and showed high specific activity when ra diolabeled with iodine. [I-127]NH2-carfentanil displayed high affinity and pronounced mu-binding selectivity with a delta/mu selectivity rat io of over 1200. The ability of [I-125]NH2- carfentanil to interact in vivo with opioid receptors was determined in mouse brain using ex viv o binding techniques. Twenty minutes after intraperitoneal injection, 0.1% of the [I-125]NH2-carfentanil injected into the mouse was present in the brain. [I-125]NH2-carfentanil specific binding was inhibited b y co-injection of naloxone or morphine while naltrindole, a delta-sele ctive antagonist, was unable to displace the bound radioligand. Autora diographic experiments revealed a heterogeneous distribution of [I-125 ]NH2-carfentanil specific binding sites, maximal binding occurred in a reas with high densities of mu receptors. Peripherally administered io do-NH2-carfentanil selectively labelled central mu opioid receptors in mouse indicating great potential for single photon emission computed tomography studies.