RenaSci is a leading provider of ex vivo receptor occupancy studies in rats and mice. Our dedicated team of experts have been conducting in vitro receptor binding assays and ex vivo occupancy studies for more than 20 years. We have the expertise to design bespoke studies to meet clients’ precise needs by developing novel assays using custom-synthesised radioligands. Alternatively, we can provide off the shelf assays using commercially available radioligands ([3H] and [125I]) for well-characterised neurotransmitter receptors and uptake sites.
Ex vivo receptor occupancy is a valuable technique in the drug discovery pathway for demonstrating target engagement of centrally penetrant compounds. Alternatively it can be used to obtain a pharmacological profile of binding sites associated with adverse side-effects such as drug abuse liability. This technique provides a link between in vitro activity and in vivo efficacy at considerably lower costs than those associated with in vivo imaging techniques.
At RenaSci ex vivo receptor occupancy studies can be undertaken either as stand-alone or subsequent to in vivo studies eg binge eating or IVSA and can be used to determine:
In ex vivo occupancy studies, the test compound or vehicle is administered to the animal peripherally. The level of in vivo receptor occupancy by test compound is subsequently measured ex vivo in a radioligand binding assay:
Radioligand receptor binding assays are extremely powerful tools for studying receptors and to characterize the binding of a drug to its target receptor, providing an important contribution to drug screening and development programmes.
There are three types of in vitro radioligand binding assays: competition, saturation and kinetic, all of which can be performed at RenaSci either in recombinant cell lines or using native tissue from rat and mouse brains (either in membrane preparations or in tissue slices).
Competition radioligand binding assays are used to determine the affinity (Ki value) of non radioactive ligands for receptors or uptake sites in membrane preparations or using autoradiography. The affinity of the ligand for the receptor is measured indirectly by measuring the ability to compete and inhibit the binding of radioligand to its receptor.
Saturation binding assays are performed to determine the affinity (Kd) of a radioligand for a receptor and the density (Bmax) of a specific receptor in membrane preparations or using autoradiography.
Binge-eating is associated with decreased D1 receptor density and increased μ-opioid receptor density in the striatum.
RenaSci also has the expertise to undertake functional pharmacological activity assays; by assessing receptor function using [35S] GTPgammaS binding or by measuring uptake into rat and mouse synaptosomes.
Dipyridamole is a moderately potent inhibitor of adenosine uptake into rat cortical synaptosomes.
If you are interested in any of our receptor binding services, please get in touch to find out more.
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