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

Five bis-benzamidines were screened towards murine magnesium deficiency-dependent audiogenic seizures, unravelling two compounds with efficacious doses 50 (ED50) less than 10 mg/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 (ED50 = 49 mg/kg) and at 4 mu g/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 (ED50 = 6 mg/kg) and on H-3-TC-binding to a rodent cerebral preparation (IC50 = 1.4 mu M). Taken as a whole, present data emphasise the suitability of bis-benzamidines as templates for designing brain protective compounds. (c) 2010 Elsevier Masson SAS. All rights reserved.