Journal article
Synthesis and binding studies of epibatidine analogues as ligands for the nicotinic acetylcholine receptors.
- Mu L Center for Radiopharmaceutical Sciences, Swiss Federal Institute of Technology Zurich, Paul Scherrer Institute, Villigen and University Hospital of Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
- Drandarov K
- Bisson WH
- Schibig A
- Wirz C
- Schubiger PA
- Westera G
- 2006-03-21
Published in:
- European journal of medicinal chemistry. - 2006
Animals
Bridged Bicyclo Compounds, Heterocyclic
Ligands
Magnetic Resonance Spectroscopy
Mice
Molecular Structure
Neurons
Pyridines
Rats
Receptors, Nicotinic
Structure-Activity Relationship
English
Neuronal nicotinic acetylcholine receptors (nAChRs) are transmembrane ligand-gated ion channels. Recent research demonstrated that selective nAChR ligands may have therapeutic potential in a number of CNS diseases and disorders. The alkaloid epibatidine is a highly potent non-opioid analgesic and nAChR agonist, but too toxic to be a useful ligand. To develop ligands selective for distinct nAChR subtypes and with reduced toxicity, a series of epibatidine and homoepibatidine analogues were synthesized. (+/-)-8-Methyl-3-(pyridin-3-yl)-8-azabicyclo[3,2,1]oct-2-ene, showed high affinity towards alpha4beta2 (Ki=2 nM), subtype selectivity (alpha4beta2/alpha7 affinity ratio>100) and relatively low toxicity in mice and can be labeled with 11C and 18F as positron emission tomography (PET) tracers for imaging of nAChRs.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.ejmech.2006.01.015
- PMID 16545497
- Persistent URL
- https://sonar.rero.ch/global/documents/233823
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