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 (ED(50)) less than 10mgkg. 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 mgkg) and at 4 microgkg 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 mgkg) 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.