2-Oxo-2H-Pyrimido[2,1-b]Benzothiazoles Inhibit Brain Benzodiazepine Receptor Binding in vitro

Abstract
2-Oxo-2H-pyrimido[2,1-b]benzothiazole derivatives were found to inhibit the in vitro binding of 3H-Ro 15-1788 (3H-flumazenil) to rat cortical benzodiazepine receptors with IC50 values in the range of 0.7–13 μmol/l. The most potent compound, 2-oxo-4-phenyl-2H-pyrimido[2,1-b]- benzothiazole showed a similar potency to inhibit 3H-Ro 15-1788 binding to membrane preparations of rat brain cortex, cerebellum and hippocampus as well as to various subunit combinations of recombinant human γ-aminobutyric acidA/benzodiazepine receptors. Scatchard plot analysis showed that 2-oxo-4-phenyl-2H-pyrimido[2,1-b]benzothiazole is a competitive inhibitor of 3H-Ro 15-1788 binding to rat brain cortical membrane preparations.