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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.
- 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.)
- Subjects :
- Animals
Anticonvulsants chemistry
Anticonvulsants pharmacology
Anticonvulsants therapeutic use
Anticonvulsants toxicity
Antioxidants
Benzamidines chemical synthesis
Benzamidines therapeutic use
Benzamidines toxicity
Binding Sites drug effects
Body Temperature drug effects
Brain metabolism
Mice
Models, Molecular
Molecular Conformation
Motor Activity drug effects
N-Methylaspartate metabolism
N-Methylaspartate pharmacology
Neuroprotective Agents chemistry
Neuroprotective Agents pharmacology
Neuroprotective Agents therapeutic use
Neuroprotective Agents toxicity
Phencyclidine chemistry
Phencyclidine metabolism
Receptors, N-Methyl-D-Aspartate metabolism
Seizures chemically induced
Seizures metabolism
Seizures physiopathology
Benzamidines pharmacology
Brain drug effects
N-Methylaspartate antagonists & inhibitors
Phencyclidine analogs & derivatives
Seizures drug therapy
Subjects
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