- Antiseizure activity of novel gamma-aminobutyric acid (A) receptor subtype-selective benzodiazepine analogues in mice and rat models.
Antiseizure activity of novel gamma-aminobutyric acid (A) receptor subtype-selective benzodiazepine analogues in mice and rat models.
Journal of medicinal chemistry (2009-03-12)
Felix M Rivas, James P Stables, Lauren Murphree, Rahul V Edwankar, Chitra R Edwankar, Shengming Huang, Hiteshkumar D Jain, Hao Zhou, Samarpan Majumder, Subramanian Sankar, Bryan L Roth, Joachim Ramerstorfer, Roman Furtmüller, Werner Sieghart, James M Cook
PMID19275170
摘要
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.