Antiseizure Activity of Novel γ-Aminobutyric Acid (A) Receptor Subtype-Selective Benzodiazepine Analogues in Mice and Rat Models
- Rivas, Felix M.
- Stables, James P.
- Murphree, Lauren
- Edwankar, Rahul V.
- Edwankar, Chitra R.
- Huang, Shengming
- Jain, Hiteshkumar D.
- Zhou, Hao
- Majumder, Samarpan
- Sankar, Subramanian
- Roth, Bryan L.
- Ramerstorfer, Joachim
- Furtmüller, Roman
- Sieghart, Werner
- Cook, James M.
Publication date
January 2009
DOIAbstract
The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for α2β3γ2 and α3β3γ2 GABAA-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
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