Synthesis and In Vitro Evaluation of Novel Nortropane Derivatives as Potential Radiotracers for Muscarinic M2 Receptors
Joint Authors
Booij, Jan
van Eck-Smit, Berthe L. F.
Knol, Remco J. J.
Janssen, Anton G. M.
de Bruin, Kora
van den Bos, Jan C.
Source
International Journal of Molecular Imaging
Issue
Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2011-06-13
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
Disturbances of the cerebral cholinergic neurotransmitter system are present in neurodegenerative disorders.
SPECT or PET imaging, using radiotracers that selectively target muscarinic receptor subtypes, may be of value for in vivo evaluation of such conditions.
6β-acetoxynortropane, a potent muscarinic M2 receptor agonist, has previously demonstrated nanomolar affinity and high selectivity for this receptor.
Based on this compound we synthesized four nortropane derivatives that are potentially suitable for SPECT imaging of the M2 receptor.
6β-acetoxynortropane and the novel derivatives were tested in vitro for affinity to the muscarinic M1−3 receptors.
The original 6β-acetoxynortropane displayed high affinity (Ki=70–90 nM) to M2 receptors and showed good selectivity ratios to the M1 (65-fold ratio) and the M3 (70-fold ratio) receptors.
All new derivatives showed reduced affinity to the M2 subtype and loss of subtype selectivity.
It is therefore concluded that the newly synthesized derivatives are not suitable for human SPECT imaging of M2 receptors.
American Psychological Association (APA)
Knol, Remco J. J.& van den Bos, Jan C.& Janssen, Anton G. M.& de Bruin, Kora& van Eck-Smit, Berthe L. F.& Booij, Jan. 2011. Synthesis and In Vitro Evaluation of Novel Nortropane Derivatives as Potential Radiotracers for Muscarinic M2 Receptors. International Journal of Molecular Imaging،Vol. 2011, no. 2011, pp.1-7.
https://search.emarefa.net/detail/BIM-492345
Modern Language Association (MLA)
Knol, Remco J. J.…[et al.]. Synthesis and In Vitro Evaluation of Novel Nortropane Derivatives as Potential Radiotracers for Muscarinic M2 Receptors. International Journal of Molecular Imaging No. 2011 (2011), pp.1-7.
https://search.emarefa.net/detail/BIM-492345
American Medical Association (AMA)
Knol, Remco J. J.& van den Bos, Jan C.& Janssen, Anton G. M.& de Bruin, Kora& van Eck-Smit, Berthe L. F.& Booij, Jan. Synthesis and In Vitro Evaluation of Novel Nortropane Derivatives as Potential Radiotracers for Muscarinic M2 Receptors. International Journal of Molecular Imaging. 2011. Vol. 2011, no. 2011, pp.1-7.
https://search.emarefa.net/detail/BIM-492345
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-492345