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Abstract
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Background: Despite introduction of modern antiepileptic drugs, 30% of epileptic patients are still drug resistant.
Remarkable three-dimensional spatial structure of AdCA, yet the simplicity of the molecule, makes AdCA a
promising lead compound. Methods: Sedative/motor impairment and 24-h mortality rate of AdCA were
determined in mice. Impact of AdCA on (1) threshold and occurrence of clonic seizures induced by PTZ in mice, (2)
incidence of tonic seizures induced by MES in mice, and (3) incidence of generalized seizures and duration of
evoked afterdischarges in amygdala-kindled rats, were determined. The role of benzodiazepine receptors in the
AdCA effect on clonic seizure threshold was also assessed. Results: AdCA showed sedative effect (TD50 = 224.5
[190.2-289.9] mg/kg). LD50 = 805.5 (715.2–988.1) mg/kg was obtained for AdCA. The compound increased PTZ
seizure threshold from 180 mg/kg (p < 0.05) and also inhibited the incidence of clonic seizures (ED50 = 256.3
[107.4-417.3] mg/kg). AdCA also decreased afterdischarge duration (p < 0.01) and the incidence of generalized
seizures (ED50 < 50 mg/kg) in the kindled rats. However, AdCA did not protect mice against tonic seizures induced
by MES. The benzodiazepine receptor antagonist flumazenil prevented the increase of seizure threshold by AdCA.
Conclusion: AdCA possesses anticonvulsant activity in kindling and PTZ models through the activation of
benzodiazepine/GABAA receptors with acceptable therapeutic index.
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