3-Amino-beta-carboline derivatives and the benzodiazepine receptor. Synthesis of a selective antagonist of the sedative action of diazepam

R H Dodd; C Ouannès; L P de Carvalho; A Valin; P Venault; G Chapouthier; J Rossier; P Potier

doi:10.1021/jm00383a024

3-Amino-beta-carboline derivatives and the benzodiazepine receptor. Synthesis of a selective antagonist of the sedative action of diazepam

J Med Chem. 1985 Jun;28(6):824-8. doi: 10.1021/jm00383a024.

Authors

R H Dodd, C Ouannès, L P de Carvalho, A Valin, P Venault, G Chapouthier, J Rossier, P Potier

PMID: 2989520
DOI: 10.1021/jm00383a024

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carbolines / chemical synthesis*
Carbolines / pharmacology
Convulsants / pharmacology
Diazepam / antagonists & inhibitors*
In Vitro Techniques
Indoles / chemical synthesis*
Male
Mice
Papio
Rats
Rats, Inbred Strains
Receptors, GABA-A / drug effects*
Structure-Activity Relationship

Substances

Carbolines
Convulsants
Indoles
Receptors, GABA-A
beta-carboline-3-carboxylic acid ethyl ester
beta-carboline-3-carboxylic acid methyl ester
Diazepam