Document Report Card

ID: ALA1153371

Journal: J Med Chem

Title: Antiseizure activity of novel gamma-aminobutyric acid (A) receptor subtype-selective benzodiazepine analogues in mice and rat models.

Authors: Rivas FM, Stables JP, Murphree L, Edwankar RV, Edwankar CR, Huang S, Jain HD, Zhou H, Majumder S, Sankar S, Roth BL, Ramerstorfer J, Furtmüller R, Sieghart W, Cook JM.

Abstract: The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, ip) were observed for compounds 2-4 in the subcutaneous metrazole seizure (scMET) test. In rats, orally (po) the TI was >5 to 105. These compounds represent novel leads in the search for anticonvulsants devoid of sedative, ataxic, and amnestic side effects.

CiteXplore: 19275170

DOI: 10.1021/jm801652d