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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anticonvulsants / chemical synthesis*
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Anticonvulsants / pharmacology
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Anticonvulsants / toxicity
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Benzodiazepines / chemical synthesis*
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Benzodiazepines / pharmacology
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Benzodiazepines / toxicity
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Convulsants
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Hippocampus / drug effects
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Hippocampus / physiopathology
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Kindling, Neurologic / drug effects
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Ligands
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Mice
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Pentylenetetrazole
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Rats
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Receptors, GABA-A / metabolism*
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Seizures / chemically induced
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Seizures / drug therapy
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Structure-Activity Relationship
Substances
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Anticonvulsants
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Convulsants
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Ligands
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Receptors, GABA-A
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Benzodiazepines
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Pentylenetetrazole