Antiseizure Activity of Novel γ-Aminobutyric Acid (A) Receptor Subtype-Selective Benzodiazepine Analogues in Mice and Rat Models
- 10 March 2009
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 52 (7) , 1795-1798
- https://doi.org/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 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.Keywords
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