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.
Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anticonvulsants / chemistry
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Anticonvulsants / pharmacology
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Anticonvulsants / therapeutic use
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Anticonvulsants / toxicity
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Antioxidants
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Benzamidines / chemical synthesis
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Benzamidines / pharmacology*
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Benzamidines / therapeutic use
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Benzamidines / toxicity
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Binding Sites / drug effects
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Body Temperature / drug effects
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Brain / drug effects*
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Brain / metabolism
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Mice
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Models, Molecular
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Molecular Conformation
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Motor Activity / drug effects
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N-Methylaspartate / antagonists & inhibitors*
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N-Methylaspartate / metabolism
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N-Methylaspartate / pharmacology
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology
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Neuroprotective Agents / therapeutic use
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Neuroprotective Agents / toxicity
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Phencyclidine / analogs & derivatives*
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Phencyclidine / chemistry
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Phencyclidine / metabolism
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Receptors, N-Methyl-D-Aspartate / metabolism
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Seizures / chemically induced
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Seizures / drug therapy*
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Seizures / metabolism
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Seizures / physiopathology
Substances
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1,2-ethane bis-1-amino-4-benzamidine
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Anticonvulsants
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Antioxidants
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Benzamidines
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Neuroprotective Agents
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Receptors, N-Methyl-D-Aspartate
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N-Methylaspartate
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tenocyclidine
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Phencyclidine
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benzamidine