BINDING OF A NEW OPIATE ANTAGONIST, NALMEFENE, TO RAT-BRAIN MEMBRANES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 7  (4) , 175-177
Abstract
Nalmefene (6-methylene-naltrexone) is a potent, orally active, opiate antagonist. IC50 [median inhibitory concentration] were obtained for nalmefene, naloxone and naltrexone using radiolabeled prototype ligands for .mu., .kappa. and .delta. receptors in homogenates of rat brain minus cerebellum. Nalmefene antagonized the bindings of [3H]-dihydromorphine, [3H]-ethylketocyclazocine and [3H]-D-ala-D-leu enkephalin with IC50 in the low nanomolar range. At the central .mu. receptor, nalmefene bound with an IC50 of 1.0 nM, equal to that of naltrexone and approximately 4 times lower than that of naloxone. All 3 antagonists had Na indices < 1.0. Nalmefene is evidently a universal opiate antagonist, has no agonist character at the central .mu. site and binds more effectively to central opiate receptors than either naloxone or naltrexone.