3-Amino-beta-carboline derivatives and the benzodiazepine receptor. Synthesis of a selective antagonist of the sedative action of diazepam.
Seven 3-N-substituted derivatives of 3-amino-beta-carboline were synthesized and their affinities for the benzodiazepine receptor were assessed in vitro. Two compounds, 3-(ethylamino)-beta-carboline and 3-[(methoxycarbonyl)amino]-beta-carboline (beta-CMC), showing IC50 values of 460 and 71 nM, respectively, were selected for in vivo studies. The former compound showed long-lasting proconvulsant activity in Papio papio baboons while beta-CMC was shown in mice to selectively antagonize the sedative effects of diazepam without exhibiting convulsant, proconvulsant, or anxiogenic activity by itself.
Dodd
R H
RH
Ouannès
C
C
de Carvalho
L P
LP
Valin
A
A
Venault
P
P
Chapouthier
G
G
Rossier
J
J
Potier
P
P
D000818:Animals; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D003975:Diazepam / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis*; D008297:Male; D051379:Mice; D010215:Papio; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013329:Structure-Activity Relationship
D002243:Carbolines; D003292:Convulsants; D007211:Indoles; D011963:Receptors, GABA-A; C024915:beta-carboline-3-carboxylic acid ethyl ester; C036150:beta-carboline-3-carboxylic acid methyl ester; D003975:Diazepam