Pharmacological evaluation of an [123I] labelled imidazopyridine-3-acetamide for the study of benzodiazepine receptors

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dc.contributor.authorMattner, Fen_AU
dc.contributor.authorMardon, Ken_AU
dc.contributor.authorLoc'h, Cen_AU
dc.contributor.authorKatsifis, Aen_AU
dc.date.accessioned2014-11-21T00:30:41Zen_AU
dc.date.available2014-11-21T00:30:41Zen_AU
dc.date.issued2006-02-07en_AU
dc.date.statistics2014-11-21en_AU
dc.description.abstractIn vitro binding of the iodinated imidazopyridine, N′,N′-dimethyl-6-methyl-(4′-[123I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide [123I]IZOL to benzodiazepine binding sites on brain cortex, adrenal and kidney membranes is reported. Saturation experiments showed that [123I]IZOL, bound to a single class of binding site (nH = 0.99) on adrenal and kidney mitochondrial membranes with a moderate affinity (Kd = 30 nM). The density of binding sites was 22 ± 6 and 1.2 ± 0.4 pmol/mg protein on adrenal and kidney membranes, respectively. No specific binding was observed in mitochondrial–synaptosomal membranes of brain cortex. In biodistribution studies in rats, the highest uptake of [123I]IZOL was found 30 min post injection in adrenals (7.5% ID/g), followed by heart, kidney, lung (1% ID/g) and brain (0.12% ID/g), consistent with the distribution of peripheral benzodiazepine binding sites. Pre-administration of unlabelled IZOL and the specific PBBS drugs, PK 11195 and Ro 5-4864 significantly reduced the uptake of [123I]IZOL by 30% (p < 0.05) in olfactory bulbs and by 51–86% (p < 0.01) in kidney, lungs, heart and adrenals, while it increased by 30% to 50% (p < 0.01) in the rest of the brain and the blood. Diazepam, a mixed CBR–PBBS drug, inhibited the uptake in kidney, lungs, heart, adrenals and olfactory bulbs by 32% to 44% (p < 0.01) but with no effect on brain uptake and in blood concentration. Flumazenil, a central benzodiazepine drug and haloperidol (dopamine antagonist/sigma receptor drug) displayed no effect in [123I]IZOL in peripheral organs and in the brain. [123I]IZOL may deserve further development for imaging selectively peripheral benzodiazepine binding sites. © 2006, Elsevier Ltd.en_AU
dc.identifier.citationMattner, F., Mardon, K., Loc'h, C., & Katsifis, A. (2006). Pharmacological evaluation of an [123I] labelled imidazopyridine-3-acetamide for the study of benzodiazepine receptors. Life Sciences, 79(3), 287-294. doi:10.1016/j.lfs.2006.01.006en_AU
dc.identifier.govdoc4527en_AU
dc.identifier.issn0024-3205en_AU
dc.identifier.issue3en_AU
dc.identifier.journaltitleLife Sciencesen_AU
dc.identifier.pagination287-294en_AU
dc.identifier.urihttp://dx.doi.org/10.1016/j.lfs.2006.01.006en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/6060en_AU
dc.identifier.volume79en_AU
dc.language.isoenen_AU
dc.publisherElsevier Science Ltden_AU
dc.subjectCerebral cortexen_AU
dc.subjectBrainen_AU
dc.subjectIodine 123en_AU
dc.subjectDopamineen_AU
dc.subjectIodineen_AU
dc.subjectBlooden_AU
dc.titlePharmacological evaluation of an [123I] labelled imidazopyridine-3-acetamide for the study of benzodiazepine receptorsen_AU
dc.typeJournal Articleen_AU
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