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Search for an antidote to electroconvulsion and lethality in aminophylline-sensitized mice
A Chakrabarti1, Y Chugh, P L Sharma
1Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
Diazepam (10 mg/kg i.p.) or MK-801 (0.25 mg/kg i.p.) offered complete protection against corneal electroshock (30 mA x 0.2 s)-induced tonic seizures and lethality but failed to protect from aminophylline (150 mg/kg i.p.) + electroshock (15 mA x 0.2 s)-induced tonic seizures and lethality in mice. The diazepam (2.5 mg/kg i.p.) and MK-801 (0.25 mg/kg i.p.) combination completely protected the mice from aminophylline + electroshock-induced seizures and lethality. Sodium valproate (500 mg/kg i.p.) protected the mice from electroshock (30 mA) per se and aminophylline + electroshock (15 mA)-induced seizure and lethality. The present study established the neurosensitizing potential of a single, non-convulsive dose of aminophylline for electroconvulsion due to subthreshold intensity electroshock and demonstrated the prophylactic efficacy of sodium valproate and the synergistic therapeutic potential of diazepam and MK-801 combination against such seizure attacks.
Insights
Aminophylline sensitizes mice to electroshock seizures. Sodium valproate prevents these seizures, while a combination of diazepam and MK-801 offers synergistic protection against aminophylline-induced seizures.
Area of Science:
- Neuroscience
- Pharmacology
- Epilepsy Research
Background:
- Aminophylline can potentiate seizure susceptibility.
- Electroconvulsive thresholds can be influenced by pharmacological agents.
- Understanding drug interactions is crucial for seizure management.
Purpose of the Study:
- To investigate the neurosensitizing effect of aminophylline on electroconvulsions.
- To evaluate the protective efficacy of sodium valproate against aminophylline-enhanced seizures.
- To explore the synergistic potential of diazepam and MK-801 in preventing aminophylline-induced seizures.
Main Methods:
- Mice were administered diazepam, MK-801, sodium valproate, or combinations thereof.
- Seizure induction was achieved using corneal electroshock (CES) with varying intensities.
- Aminophylline was administered to assess its effect on seizure susceptibility and lethality.
Main Results:
- Diazepam and MK-801 alone protected against high-intensity CES but not aminophylline-potentiated seizures.
- A combination of diazepam (2.5 mg/kg) and MK-801 (0.25 mg/kg) completely protected against aminophylline + CES-induced seizures and lethality.
- Sodium valproate (500 mg/kg) demonstrated efficacy against both CES-induced seizures and aminophylline-potentiated seizures.
Conclusions:
- Aminophylline, at a non-convulsive dose, sensitizes mice to electroconvulsions induced by subthreshold electroshock.
- Sodium valproate is effective in preventing aminophylline-enhanced seizures.
- The combination of diazepam and MK-801 exhibits synergistic therapeutic potential against these seizure attacks.