Closing in on the AMPA receptor: Synthesis and evaluation of 2-acetyl-1-(4′-chlorophenyl)-6-methoxy-7-[11C]methoxy-1,2,3,4-tetrahydroisoquinoline as a potential PET tracer
| Autor: | Andrew Constanti, Erik Årstad, Roberta Caruso, Lyn S. Pilowsky, Rosaria Gitto, S.P. Hume, David R. Turton, Rabia Ahmad, Alba Chimirri, Sajinder K. Luthra |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Biodistribution Stereochemistry Clinical Biochemistry Pharmaceutical Science AMPA receptor In Vitro Techniques Ligands Biochemistry Chemical synthesis Rats Sprague-Dawley chemistry.chemical_compound In vivo Tetrahydroisoquinolines Drug Discovery Animals Carbon Radioisotopes Receptors AMPA Receptor Molecular Biology Tetrahydroisoquinoline Ligand Organic Chemistry Brain Rats chemistry Positron-Emission Tomography Molecular Medicine Preclinical imaging |
| Zdroj: | Bioorganic & Medicinal Chemistry. 14:4712-4717 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2006.03.034 |
| Popis: | 2-Acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, one of the most potent non-competitive AMPA antagonists described to date, has been labelled with carbon-11 and tritium and evaluated as a potential ligand for in vivo imaging of AMPA receptors using PET. The carbon-11 labelled compound showed good initial brain uptake in rats, but with rapid clearance and relatively homogenous distribution. In saturation binding studies, the tritiated racemic ligand was found to be highly potent with a Kd of 14.8+/-1.8 nM. We conclude that the low receptor density labelled with this compound, its rapid clearance from the CNS and low specific binding makes it unsuitable as an in vivo PET imaging agent for AMPA receptors. |
| Databáze: | OpenAIRE |
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