Benzodiazepine receptor affinity and interaction of new indole derivatives.
Recently, several derivatives, in which tryptamine, tyramine, and dopamine moieties are linked to the indole nucleus by an oxalyl bridge, were tested for their affinity and efficacy at the benzodiazepine receptor (BzR). To better define the structure-activity relationships (SAR) several phenylethylamine derivatives were also synthesized and tested for their affinity at the BzR. Compounds bearing a protic group on the aromatic system of the side chain show a pharmacological profile of inverse agonist, while the products lacking this group behave as partial agonist. We now report the affinity data at the BzR of new compounds in which the distance between the phenyl ring and the amide group of the side chain has been changed. The benzylamine derivatives showed a good affinity at the BzR, generally higher than that of the phenylethylamine derivatives. In this series the pharmacological profile showed to be opposite to that of the corresponding phenylethylamine derivatives, since the compounds substituted with protic groups on the phenyl ring behaved as partial agonists. Moreover, a probable interaction with the receptor site is hypothesized.
Istituto di Chimica Farmaceutica e Tossicologica dell'Università.
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A
Da Settimo
G
G
Primofiore
F
F
Da Settimo
A
A
Lucacchini
C
C
Martini
G
G
Senatore
D000818:Animals; D002417:Cattle; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007211:Indoles; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid