Abstract
Intracerebroventricular administration of the alkylating benzodiazepines irazepine or kenazepine (20 nmol) resulted in a complete protection against convulsant doses of pentylenetetrazole (PTZ) for at least one hour, and a statistically significant protection for at least two and four hours, respectively. In contrast, administration of the non-alkylating parent benzodiazepine Ro-7/1986 or diazepam (20–60 nmol) resulted in no detectable anticonvulsant effects at fifteen minutes post-injection, the earliest interval examined. These results suggest that alkylating benzodiazepines which bind to brain benzodiazepine receptors in a non-competitive (covalent) fashion in vitro may exert a long lasting anticonvulsant effect by a similar mechanism.
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