Specific inhibition of benzodiazepine receptor binding by some N-(indol-3-ylglyoxylyl)amino acid derivatives: stereoselective interactions.
Several optically active N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. IC50 values were measured and revealed that the D form of the amino acid moiety of the compounds was more potent than both the L form and racemic form, suggesting a key role of the amino acid stereochemistry on the affinity to the benzodiazepine receptors. GABA ratio and proconvulsant/convulsant data reported for the most active compounds reveal they behave as inverse agonists at the benzodiazepine receptor.
Primofiore
G
G
Istituto di Chimica Farmaceutica, Università di Pisa, Italy.
Marini
A M
AM
Da Settimo
F
F
Martini
C
C
Bardellini
A
A
Giannaccini
G
G
Lucacchini
A
A
D000596:Amino Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008968:Molecular Conformation; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
D000596:Amino Acids; D007211:Indoles; D011963:Receptors, GABA-A