The Involvement of Flumazenil, Amphetamine and Chlorpromazine in the Anticonvulsant Effect of Methanol Root Extract of Securidaca longepedunculata (Fresen) in Mice Model

Abstract

Background: Securidaca longipedunculata Fresen (Polygalaceae) is a versatile plant with a long history of use in African traditional medicine to treat various sexually transmitted infections, hernias, coughs, fever, ascariasis, constipation, headaches, rheumatism, stomach aches, malaria, tuberculosis, pain, epilepsy, and pneumonia. This study aimed to assess the potential effects of methanol root extract of Securidaca longepedunculata on seizures induced experimentally in mice and to evaluate the roles of flumazenil, amphetamine and chlorpromazine in mice. Materials and Methods: Animal behaviours were evaluated using hexobarbitone-induced sleep model, and anticonvulsant activity using picrotoxin- and pentylenetetrazole (PTZ)-induced convulsions. Attempt to understand the mode of action of the anticonvulsant activity of the plant; flumazenil (3 mg/kg), chlorpromazine, and amphetamine (3 mg/kg) were used. Results: The methanol root extract of Securidaca longepedunculata (MRESL) potentiates the sleeping time of hexobarbitone-induced hypnosis in a dose-related manner. The root extracts significantly (p<0.05) prolonged the onset and attenuated the duration of seizure in PTZ-induced at 600 mg/kg body weight and a dose-dependent manner in picrotoxin-induced seizure. However, the anticonvulsant activity of the methanol root extract of Securidaca longepedunculata was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist) in picrotoxin-induced convulsion but not in PTZ-induced seizure. Amphetamine significant potentiated anti-seizure property of the extract (p < 0.05), while co-administration of the extract (600 mg/kg) with chlorpromazine (5 mg/kg) did not protect the mice against this seizure in either model. Conclusion: The findings suggest that methanol root extract of Securidaca longepedunculata is effective in reducing the severity of seizures. This positive effect may be mediated through signaling pathways that involve benzodiazepine-activated γ-aminobutyric acid receptors and anti-seizure property of the extract was potentiated by amphetamine.