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

Årstad, E., Gitto, R., Chimirri, A., Caruso, R., Constanti, A., Turton, D., Hume, S.P., Ahmad, R., Pilowsky, L.S. and Luthra, S.K. (2006) 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. Bioorganic and Medicinal Chemistry, 14 (14). pp. 4712-4717. 10.1016/j.bmc.2006.03.034.

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DOI: 10.1016/j.bmc.2006.03.034

Abstract

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.

Item Type:Article
Uncontrolled Keywords:lutamate; AMPA; PET; Isoquinolines; Carbon-11
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2508
Journal or Publication Title:Bioorganic and Medicinal Chemistry
Deposited By:Library Staff
Deposited On:24 Nov 2011 16:20
Last Modified:24 Nov 2011 16:20

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