CHARACTERIZATION 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 [H-3]diazepam and ethyl 4H-imidazo[1,5- a][1,4]benzodiazepine-3-carboxylate ([H-3]Ro 15-1788) binding to the b enzodiazepine site of the rat brain gamma-aminobutyric acid(A) (GABA(A )) receptor in vitro with IC50 values of 400 and 680 nM, respectively. Two other naturally occurring furanocoumarins, byakangelicol and impe ratorin were significantly less potent, with IC50 values for inhibitio n of [H-3]diazepam binding of 8.0 and 12.3 mu M, respectively. Scatcha rd plot analysis showed that the inhibitory activity of phellopterin w as 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.