A combination of ketamine and diazepam synergistically controls refractory status epilepticus induced by cholinergic stimulation.

Abstract

PURPOSE:

New treatments are needed for status epilepticus (SE) that is refractory to drugs modulating GABA(A) receptors, and NMDA receptor antagonists are candidate drugs.

METHODS:

Clinically available NMDA receptor antagonist ketamine was tested for effectiveness in terminating prolonged SE induced by a combination of lithium and pilocarpine. Animals were treated 10 min after first grade 5 behavioral seizure (Racine scoring scale) by intraperitoneal administration of ketamine, diazepam, or saline. Seizure termination was determined by electroencephalogram (EEG) recordings from the hippocampus and the cortex.

RESULTS:

Animals treated with normal saline or either 20 mg/kg diazepam, or 50 mg/kg ketamine continued in SE for the next 300 min. However, combined treatment with diazepam and ketamine rapidly terminated prolonged cholinergic stimulation-induced SE. Detailed study of dose response relationships demonstrated that diazepam enhanced efficacy and potency of ketamine in terminating SE.

DISCUSSION:

This study demonstrated synergistic action of diazepam and ketamine in terminating SE. It suggests that a ketamine-diazepam combination might be a clinically useful therapeutic option for the treatment of refractory SE.

• Authors: Brandon S Martin, Jaideep Kapur
• Journal: Epilepsia (Epilepsia) Vol. 49 Issue 2 Pg. 248-55 (Feb 2008) ISSN: 0013-9580 [Print] United States
• PMID: 17941842 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Excitatory Amino Acid Antagonists
• Lithium Compounds
• Muscarinic Agonists
• Pilocarpine
• Ketamine
• Diazepam

Topics

• Animals
• Cerebral Cortex (drug effects, physiopathology)
• Diazepam (pharmacology, therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Synergism
• Drug Therapy, Combination
• Electroencephalography (statistics & numerical data)
• Excitatory Amino Acid Antagonists (pharmacology, therapeutic use)
• Hippocampus (drug effects, physiopathology)
• Ketamine (pharmacology, therapeutic use)
• Lithium Compounds
• Male
• Muscarinic Agonists
• Pilocarpine
• Rats
• Rats, Sprague-Dawley
• Status Epilepticus (chemically induced, physiopathology, prevention & control)
• Treatment Outcome