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1,2-ethane bis-1-amino-4-benzamidine is active against several brain insult and seizure challenges through anti-NMDA mechanisms targeting the 3H-TCP binding site and antioxidant action.

Authors :
Vamecq J
Maurois P
Pages N
Bac P
Stables JP
Gressens P
Stanicki D
Vanden Eynde JJ
Source :
European journal of medicinal chemistry [Eur J Med Chem] 2010 Jul; Vol. 45 (7), pp. 3101-10. Date of Electronic Publication: 2010 Apr 03.
Publication Year :
2010

Abstract

Five bis-benzamidines were screened towards murine magnesium deficiency-dependent audiogenic seizures, unravelling two compounds with efficacious doses 50 (ED(50)) less than 10mg/kg. They were also screened against maximal electroshock and subcutaneous pentylenetetrazole-induced seizures, and explored for superoxide -scavenging activity. 1,2-Ethane bis-1-amino-4-benzamidine (EBAB) was selected and evaluated in 6 Hz seizure test (ED(50)=49 mg/kg) and at 4 microg/kg in focal cerebral ibotenate poisoning in pups (sizes of both white and grey matter wounds were halved). EBAB was further tested on NMDA-induced seizures in mice (ED(50)=6 mg/kg) and on (3)H-TC -binding to a rodent cerebral preparation (IC(50)=1.4 microM). Taken as a whole, present data emphasise the suitability of bis-benzamidines as templates for designing brain protective compounds.<br /> (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

Details

Language :
English
ISSN :
1768-3254
Volume :
45
Issue :
7
Database :
MEDLINE
Journal :
European journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
20427101
Full Text :
https://doi.org/10.1016/j.ejmech.2010.03.044