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Anticonvulsant profile of ondansetron in rats
S Balakrishnan1, V K Bhargava, P Pandhi
1Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh-, 160012, India.
Abstract:
Recent studies have shown the involvement of 5-hydroxytryptamine (5HT) in the pathogenesis of epilepsy. Hence it was decided to investigate the effect of the 5HT3 receptor antagonist ondansetron against maximal electroshock (MES)-induced seizures in rats. Also, the anticonvulsant activity of ondansetron in combination with phenytoin and its effect on the cognitive deficits induced by phenytoin were studied. MES was induced through ear-clip electrodes using a current strength of 150 mA for 0.2 second. The index of protection was taken as the inhibition of tonic hindlimb extension. The ED25 and ED16 doses of ondansetron were combined with subanticonvulsant doses of phenytion, i.e., 6 and 3 mg/kg. The retention latencies in the passive avoidance task (PAT) were assessed on Days 1 and 21 of chronic administration of ondansetron alone, phenytoin alone, and ondansetron in combination with phenytoin. The ED50 of ondansetron was found to be 1.05 (0.51-2.2) mg/kg. The combination of ondansetron with phenytoin had a potentiating effect against MES. Also, the retention latencies in the PAT of ondansetron alone and ondansetron in combination with phenytoin were significantly higher than that of phenytoin alone. Thus, ondansetron has potent anticonvulsant activity in rats and further potentiates the anticonvulsant activity of phenytoin. Also, it attenuates the cognitive dysfunction induced by phenytoin and merits further research for its mechanisms.
Insights
Ondansetron, a 5-hydroxytryptamine (5HT)3 receptor antagonist, shows potent anticonvulsant activity in rats. It enhances phenytoin
Area of Science:
- Neuroscience
- Pharmacology
- Epilepsy Research
Background:
- Emerging evidence implicates 5-hydroxytryptamine (5HT) in epilepsy pathogenesis.
- 5HT3 receptor antagonists represent a potential therapeutic avenue for seizure disorders.
Purpose of the Study:
- To evaluate the anticonvulsant efficacy of ondansetron against maximal electroshock (MES)-induced seizures in rats.
- To investigate the synergistic anticonvulsant effects of ondansetron combined with phenytoin.
- To assess the impact of ondansetron on phenytoin-induced cognitive deficits.
Main Methods:
- Maximal electroshock (MES) seizures were induced in rats.
- Anticonvulsant activity was assessed by inhibition of tonic hindlimb extension.
- Ondansetron was administered alone and in combination with sub-effective doses of phenytoin.
- Cognitive function was evaluated using the passive avoidance task (PAT).
Main Results:
- The median effective dose (ED50) of ondansetron was determined to be 1.05 mg/kg.
- Ondansetron demonstrated significant anticonvulsant activity against MES-induced seizures.
- Combination therapy with ondansetron and phenytoin exhibited a potentiating effect on anticonvulsant activity.
- Ondansetron administration, alone and combined with phenytoin, improved retention latencies in the PAT compared to phenytoin alone.
Conclusions:
- Ondansetron possesses significant anticonvulsant properties in a rat model.
- Ondansetron enhances the anticonvulsant efficacy of phenytoin.
- Ondansetron may mitigate cognitive dysfunction associated with phenytoin treatment, warranting further mechanistic investigation.