title: Development of ligands for in vivo imaging of cerebral nicotinic receptors.
abstract: Nicotinic acetylcholine receptors (nAChRs) mediate a variety of brain functions. Findings from postmortem studies and clinical investigations have implicated them in the pathophysiology and treatment of Alzheimer's and Parkinson's diseases and other CNS disorders (e.g. Tourette's syndrome, epilepsy, nicotine dependence). Therefore, it ultimately might be useful to image nAChRs noninvasively for diagnosis, for studies on how changes in nAChRs might contribute to cerebral disorders, for development of therapies targeted at nAChRs, and to monitor the effects of such treatments. To date, only (S)-(-)-nicotine, radiolabeled with 11C, has been used for external imaging of nAChRs in human subjects. Since this radiotracer presents drawbacks, new ligands, with more favorable properties, have been synthesized and tested. Three general classes of compounds, namely, nicotine and its analogs, epibatidine and related compounds, and 3-pyridyl ether compounds, including A-85380, have been evaluated. Analogs of A-85380 appear to be the most promising candidates because of their low toxicity and high selectivity for the alpha4beta2 subtype of nAChRs.
authors.affiliation: Department of Medical Pharmacology, Karolinska Institute, Huddinge Hospital, Sweden. wiebke.sihver@pet.uu.se
authors.forename: W
authors.initials: W
authors.lastname: Sihver
authors.forename: A
authors.initials: A
authors.lastname: Nordberg
authors.forename: B
authors.initials: B
authors.lastname: Långström
authors.forename: A G
authors.initials: AG
authors.lastname: Mukhin
authors.forename: A O
authors.initials: AO
authors.lastname: Koren
authors.forename: A S
authors.initials: AS
authors.lastname: Kimes
authors.forename: E D
authors.initials: ED
authors.lastname: London
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001931:Brain Mapping; D006801:Humans; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009538:Nicotine / Q000031:analogs & derivatives*; D011978:Receptors, Nicotinic / Q000502:physiology*; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine