Effect of beta-carboline derivatives on the binding of L-tryptophan and diazepam to bovine and human albumin.
The effects of 12 beta-carboline derivatives on the binding of L-tryptophan and diazepam to bovine and human albumin have been investigated to seek similarities between the indole binding site on albumin and the benzodiazepine receptor in the brain. The binding of L-tryptophan and diazepam was measured at 37 degrees and pH 7.4 by equilibrium dialysis. Norharmane was the most potent inhibitor of the binding of L-tryptophan and diazepam to both bovine and human albumin. The kinetics of the inhibitory effects of several of the beta-carbolines were studied. Norharmane decreased the value (n) for the number of binding sites for the binding of L-tryptophan to both bovine and human albumin. Norharmane and harmane decreased the apparent association (Ka) but increased n for the interaction of diazepam with bovine albumin. Norharmane also had a similar effect on the binding of diazepam to human albumin. The similarities between the inhibitory effects of the beta-carbolines on the binding of L-tryptophan and diazepam to albumin and the affinity of the beta-carbolines for the central benzodiazepine receptor point to some common structural requirements for binding to the receptor and to albumin.
Fenerty
C A
CA
Department of Pharmacology and Therapeutics, University of Liverpool, U.K.
Lindup
W E
WE
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002243:Carbolines / Q000494:pharmacology*; D002417:Cattle; D003975:Diazepam / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000378:metabolism; D007700:Kinetics; D011485:Protein Binding / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D014364:Tryptophan / Q000378:metabolism*
D000418:Albumins; D002243:Carbolines; D007211:Indoles; D011963:Receptors, GABA-A; C024915:beta-carboline-3-carboxylic acid ethyl ester; D014364:Tryptophan; D003975:Diazepam