In vitro Receptor Autoradiogarphy, and In vivo/Ex vivo Receptor Occupancy
Tests used for CNS drug development such as receptor autoradiography, ex vivo and in vivo receptor occupancy (RO) offer a simple yet powerful way to:
Beta-imaging technology, developed by Biospace, France, and used by scientists at PsychoGenics, significantly shortens the time needed for assessment of specific binding in the brain (hours versus weeks for tritiated ligands), which makes it possible to use ex vivo RO (an assay that could provide crucially important preclinical data for preclinical and clinical candidate selection) as a screening tool.
Receptor autoradiography to calculate Ki values on endogenously expressed receptors
Figure 2. High correspondence between behaviorally active doses of sazetidine in the forced swim test (Fig 2A) and ɑ4β2 nicotinic acetylcholine receptor (nAChR) occupancy in the brain (Fig 2B). Specifically, sazetidine was inactive in the forced swim test at 0.3 mg/kg (i.p) and showed very low receptor occupancy at this dose (<10%). In contrast, doses of sazetidine (1 and 3 mg/kg, i.p.) that produced robust behavioral activity in the forced swim test, corresponded with high levels of occupancy at the ɑ4β2 nAChRs (~40% and ~90% respectively).
Currently, we have developed protocols for ex vivo receptor occupancy and receptor autoradiography studies for the following targets: