2-Oxo-2H-Pyrimido[2,1-b]benzothiazoles inhibit brain benzodiazepine receptor binding in vitro.
2-Oxo-2H-pyrimido[2,1-b]benzothiazole derivatives were found to inhibit the in vitro binding of (3)H-Ro 15-1788 ((3)H-flumazenil) to rat cortical benzodiazepine receptors with IC(50) values in the range of 0.7-13 micromol/l. The most potent compound, 2-oxo-4-phenyl-2H-pyrimido[2,1-b]- benzothiazole showed a similar potency to inhibit (3)H-Ro 15-1788 binding to membrane preparations of rat brain cortex, cerebellum and hippocampus as well as to various subunit combinations of recombinant human gamma-aminobutyric acid(A)/benzodiazepine receptors. Scatchard plot analysis showed that 2-oxo-4-phenyl-2H-pyrimido[2,1-b]benzothiazole is a competitive inhibitor of (3)H-Ro 15-1788 binding to rat brain cortical membrane preparations.
Ai
J
J
Department of Psychopharmacology, Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark. jinglu.ai@shh.hosp.dk
Wang
X
X
Wahe
H
H
Fomum
Z T
ZT
Sterner
O
O
Nielsen
M
M
Witt
M R
MR
D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism*; D005442:Flumazenil / Q000378:metabolism*; D018757:GABA Modulators / Q000378:metabolism*; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*
D052160:Benzothiazoles; D018757:GABA Modulators; D011963:Receptors, GABA-A; D013844:Thiazoles; D005442:Flumazenil; C005465:benzothiazole