New Nortropane Derivatives for Imaging Muscarinic M2 Receptors
Author Information
Author(s): Remco J. J. Knol, Jan C. van den Bos, Anton G. M. Janssen, Kora de Bruin, Berthe L. F. van Eck-Smit, Jan Booij
Primary Institution: Medical Center Alkmaar
Hypothesis
Can new nortropane derivatives be synthesized to selectively target muscarinic M2 receptors for SPECT imaging?
Conclusion
The newly synthesized nortropane derivatives are not suitable for human SPECT imaging of M2 receptors due to reduced affinity and selectivity.
Supporting Evidence
- 6β-acetoxynortropane showed high affinity for M2 receptors with selectivity ratios of 65 and 70 for M1 and M3 receptors, respectively.
- All new derivatives displayed reduced affinity to the M2 subtype and loss of subtype selectivity.
- The original compound had a K_i of 71.6 ± 4.8 nM for M2 receptors, while the derivatives had K_i values in the micromolar range.
Takeaway
Scientists made new versions of a compound to help see brain receptors in scans, but these new versions didn't work as well as hoped.
Methodology
Four nortropane derivatives were synthesized and tested for their affinity to muscarinic M1–3 receptors using in vitro competitive binding assays.
Limitations
The synthesized derivatives showed significantly lower affinity and selectivity for the M2 receptor compared to the original compound.
Digital Object Identifier (DOI)
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