High affinity of the naturally-occurring biflavonoid, amentoflavon, to brain benzodiazepine receptors in vitro.
In a search for pharmacologically-active ingredients in the plant extract Karmelitter Geist, we have isolated and identified a high-affinity benzodiazepine receptor ligand, amentoflavon. Amentoflavon binds in a mix-type competitive and non-competitive manner to brain benzodiazepine receptors with an IC50-value of 6 nM in vitro, comparable to the affinity of diazepam. Amentoflavon shows a GABA ratio of 1.4 at 0 degrees and increases 35S-TBPS binding by 12% (60 min incubation at 25 degrees), which indicates a partial agonistic effect on benzodiazepine receptors. The substance does not influence the binding of a variety of other brain receptor ligands. Amentoflavon does not inhibit 3H-flunitrazepam-binding to brain benzodiazepine receptors following i.v. administration in the mouse in vivo, and it is therefore not likely that amentoflavon is responsible for any pharmacological effect of Karmelitter Geist.
Nielsen
M
M
Psychopharmacological Research Laboratory, Sct. Hans Hospital, Roskilde, Denmark.
Frøkjaer
S
S
Braestrup
C
C
D000818:Animals; D044946:Biflavonoids; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*
D044946:Biflavonoids; D005419:Flavonoids; D011963:Receptors, GABA-A; C011164:amentoflavone