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 μg/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 3H-TC -binding to a rodent cerebral preparation (IC50 = 1.4 μM). Taken as a whole, present data emphasise the suitability of bis-benzamidines as templates for designing brain protective compounds.

Graphical abstract1,2-Ethane bis-1-amino-4-benzamidine [EBAB] (R1 = R2 = H) presented with efficacy against various types of seizures and brain wounds, along with inhibitory properties towards 3H-TCP binding to NMDA receptor (IC50 = 1.4 mM).Figure optionsDownload full-size imageDownload as PowerPoint slide