title: 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.
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.
authors.affiliation: Inserm Univ 045131, Faculty of Medicine, Research Branch, University of Lille 2, France. joseph.vamecq@inserm.fr
authors.forename: Joseph
authors.initials: J
authors.lastname: Vamecq
authors.forename: Pierre
authors.initials: P
authors.lastname: Maurois
authors.forename: Nicole
authors.initials: N
authors.lastname: Pages
authors.forename: Pierre
authors.initials: P
authors.lastname: Bac
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Dimitri
authors.initials: D
authors.lastname: Stanicki
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Vanden Eynde
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D000975:Antioxidants; D001550:Benzamidines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D001665:Binding Sites / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C551371:1,2-ethane bis-1-amino-4-benzamidine; D000927:Anticonvulsants; D000975:Antioxidants; D001550:Benzamidines; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C012058:tenocyclidine; D010622:Phencyclidine; C032157:benzamidine