Aspects of Preclinical GABA(A)R subtype drug discovery platform

Question 1

Steps for identification of novel GABA(A)R subtype-selective benzodiazepines

Answer 1

1) compound synthesis
2) displacement of 3H-flunitrazepam from rat membranes
3) displacement of 3H-flunitrazepam from cell lines expressing recombinant human GABA(A)Rs
4) functional electrophysiological studies with cell lines expressing recombinant GABA(A)Rs and neuronal GABA(A)Rs
5) appropriate pharmacokinetics; CNS receptor occupancy, changes in EEG activity (Mouse/Rat)
6) behavioural studies