title: [125I]iodoclonazepam, a specific high affinity radioligand for the identification of BZ1 and BZ2 sites in rat brain.
abstract: Binding of the radioligand [125I]iodoclonazepam to three different areas of rat brain (cerebellum, hippocampus and striatum) has been characterised. In all three regions binding is rapid, saturable and of high affinity (cerebellum Bmax = 1.49 +/- 0.3 pmol/mg of protein, Kd = 0.39 +/- 0.06 nM; hippocampus Bmax = 1.5 +/- 0.14 pmol/mg of protein, Kd = 0.38 +/- 0.6 nM and striatum Bmax = 0.53 +/- 0.1 pmol/mg of protein, Kd = 0.34 +/- 0.03 nm, n = 3). In all regions only one population of sites was apparent. However, competition for [125I]iodoclonazepam sites by a series of benzodiazepine agonists and antagonists showed some regional differences. The BZ1 selective compounds zolpidem and CL218,872 showed a 4.3-fold and 5.2-fold selectivity for cerebellar binding sites respectively. We conclude that [125I]iodoclonazepam is a novel, high affinity ligand which recognises both BZ1 and BZ2 classes of receptor and should be a useful addition to the panel of benzodiazepine ligands currently available.
authors.affiliation: Department of Biochemistry, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, U.K.
authors.forename: N P
authors.initials: NP
authors.lastname: Gillard
authors.forename: K
authors.initials: K
authors.lastname: Quirk
authors.forename: C I
authors.initials: CI
authors.lastname: Ragan
authors.forename: R M
authors.initials: RM
authors.lastname: McKernan
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008024:Ligands; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D007457:Iodine Radioisotopes; D008024:Ligands; D011963:Receptors, GABA-A; C058316:7-iodoclonazepam; D002998:Clonazepam