Characterisation of the furanocoumarin phellopterin as a rat brain benzodiazepine receptor partial agonist in vitro.
Phellopterin, a naturally occurring furanocoumarin found in the roots of Angelica dahurica, inhibits [3H]diazepam and ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate ([3H]Ro 15-1788) binding to the benzodiazepine site of the rat brain gamma-aminobutyric acidA (GABAA) receptor in vitro with IC50 values of 400 and 680 nM, respectively. Two other naturally occurring furanocoumarins, byakangelicol and imperatorin were significantly less potent, with IC50 values for inhibition of [3H]diazepam binding of 8.0 and 12.3 microM, respectively. Scatchard plot analysis showed that the inhibitory activity of phellopterin was due to competitive inhibition of the benzodiazepine ligand binding. The results of GABA- and t-butylbicyclophosphorothionate (TBPS)-shift assays suggest that phellopterin is a partial agonist of the central benzodiazepine receptors in vitro.
Dekermendjian
K
K
Department of Biochemistry, St. Hans Hospital, Roskilde, Denmark.
Ai
J
J
Nielsen
M
M
Sterner
O
O
Shan
R
R
Witt
M R
MR
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology*; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000378:metabolism; D005442:Flumazenil / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D058785:GABA-A Receptor Agonists; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D003374:Coumarins; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C104601:phellopterin; D005442:Flumazenil; C037476:tert-butylbicyclophosphorothionate; D003975:Diazepam