2. Academic Validation
  3. 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

  • J Med Chem. 2009 Apr 9;52(7):1795-8. doi: 10.1021/jm801652d.
Felix M Rivas 1,  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
Affiliations

Affiliation

  • 1 Department of Chemistry and Biochemistry, University of WisconsinsMilwaukee, Milwaukee, Wisconsin 53211, USA.
PMID: 19275170 DOI: 10.1021/jm801652d
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-123426
    GABAA receptors agonist