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Diazepam-atenolol combination antagonizes aminophylline-induced convulsions and lethality in mice
Y Chugh1, A Chakrabarti, P L Sharma
1Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
The present study was undertaken to identify protective drugs against aminophylline (240 mg/kg i.p.)-induced convulsions and lethality in mice. Diazepam (10 mg/kg) and valproic acid significantly prevented the convulsions, but were not effective in preventing mortality. Phenytoin, atropine, carbamazepine and atenolol were ineffective in protecting against convulsions and death. Ketamine gave partial protection against convulsions, but was not effective in preventing mortality. Diazepam (10 mg/kg) and atenolol (5 mg/kg) administered together gave total protection against convulsions and death. These results show that aminophylline-induced convulsions are relatively resistant to antiepileptic drugs, and that a combination of diazepam and a beta-blocker (atenolol) has potential as an anti-aminophylline agent.
Insights
This study investigated drugs to protect against aminophylline-induced seizures and death in mice. A combination of diazepam and atenolol effectively prevented both convulsions and mortality, suggesting a novel therapeutic approach.
Area of Science:
- Pharmacology
- Neuroscience
- Toxicology
Background:
- Aminophylline is a common respiratory stimulant.
- Aminophylline overdose can cause severe neurological side effects, including seizures and potentially death.
- Existing antiepileptic drugs show limited efficacy against aminophylline-induced toxicity.
Purpose of the Study:
- To identify potential therapeutic agents for aminophylline-induced convulsions and lethality.
- To evaluate the efficacy of various drugs, including diazepam, valproic acid, phenytoin, atropine, carbamazepine, atenolol, and ketamine.
- To explore combination therapies for enhanced protection.
Main Methods:
- Mice were administered a high dose of aminophylline (240 mg/kg i.p.) to induce convulsions and lethality.
- Various drugs and drug combinations were administered to assess their protective effects.
- Convulsions and mortality rates were recorded and analyzed.
Main Results:
- Diazepam and valproic acid partially protected against convulsions but not mortality.
- Phenytoin, atropine, carbamazepine, and ketamine showed minimal or no protective effects.
- A combination of diazepam (10 mg/kg) and atenolol (5 mg/kg) provided complete protection against both aminophylline-induced convulsions and death.
Conclusions:
- Aminophylline-induced seizures are relatively resistant to conventional antiepileptic drugs.
- The combination of diazepam and the beta-blocker atenolol demonstrates significant potential as a protective agent against aminophylline toxicity.
- This combination therapy warrants further investigation for clinical application in managing aminophylline overdose.