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[I] 5-Iodo-3-pyridyl ethers: syntheses and binding to neuronal nicotinic acetylcholine receptors |
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| Authors: | Hong Fan Ursula A. Scheffel Paige Rauseo Yingxian Xiao A. Semih Dogan Fuji Yokoi John Hilton Kenneth J. Kellar Dean F. Wong John L. Musachio |
| Affiliation: | a Johns Hopkins University School of Medicine, Department of Radiology, Division of Nuclear Medicine, Baltimore, MD 21287 USA b Johns Hopkins University School of Public Health, Department of Environmental Health Sciences, Baltimore, MD 21205 USA c Georgetown University Department of Pharmacology, Washington D.C. 20007, USA |
| Abstract: | Three 3-pyridyl ether nicotinic ligands-(S)-5-Iodo-3-[(2-pyrrolidinyl)-methoxy]pyridine (5-iodo-A-85865), (S)-5-Iodo-3-[1-(methyl)-2-pyrrolidinyl-methoxy]pyridine (5-Iodo-A-84543), and (S)-5-iodo-3-[1-methyl-(2-azetidinyl)-methoxy]pyridine (5-iodo-N-Me-A-85380) were labeled with I-125/I-123, and their ability to label high-affinity brain nicotinic acetylcholine receptors (nAChRs) was evaluated. The most promising ligand, [123/125I] 5-iodo-A-85865, showed approximately 65% inhibition of radioactivity uptake in thalamus in mice pretreated with cytisine. Preliminary SPECT imaging studies with [123I] 5-iodo-A-85865 revealed a distribution profile consistent with nAChRs (thalamus > frontal cortex > cerebellum) and a more rapid pharmacokinetic profile relative to azetidinyl 3-pyridyl ether based ligands. |
| Keywords: | Iodine-123 Nicotinic acetylcholine receptor SPECT |
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