Seizure suppression by adenosine A1 receptor activation in a mouse model of pharmacoresistant epilepsy.

Abstract

PURPOSE:

Because of the high incidence of pharmacoresistance in the treatment of epilepsy (20-30%), alternative treatment strategies are needed. Recently a proof-of-principle for a new therapeutic approach was established by the intraventricular delivery of adenosine released from implants of engineered cells. Adenosine-releasing implants were found to be effective in seizure suppression in a rat model of temporal lobe epilepsy. In the present study, activation of the adenosine system was applied as a possible treatment for pharmacoresistant epilepsy.

METHODS:

A mouse model for drug-resistant mesial temporal lobe epilepsy was used, in which recurrent spontaneous seizure activity was induced by a single intrahippocampal injection of kainic acid (KA; 200 ng in 50 nl).

RESULTS:

After injection of the selective adenosine A1-receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA; either 1.5 or 3 mg/kg, i.p.), epileptic discharges determined in EEG recordings were completely suppressed for a period of </=3.5 h after the injections. Seizure suppression was maintained when 8-sulfophenyltheophylline (8-SPT), a non-brain-permeable adenosine-receptor antagonist, was coinjected systemically with CCPA. In contrast, systemic injection of carbamazepine or vehicle alone did not alter the seizure pattern.

CONCLUSIONS:

This study demonstrates that activation of central adenosine A1 receptors leads to the suppression of seizure activity in a mouse model of drug-resistant epilepsy. We conclude that the local delivery of adenosine into the brain is likely to be effective in the control of intractable seizures.

• Authors: Nicolette Gouder, Jean-Marc Fritschy, Detlev Boison
• Journal: Epilepsia (Epilepsia) Vol. 44 Issue 7 Pg. 877-85 (Jul 2003) ISSN: 0013-9580 [Print] United States
• PMID: 12823569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Purinergic P1 Receptor Agonists
• Receptors, Purinergic P1
• 2-chloro-N(6)cyclopentyladenosine
• Adenosine
• Kainic Acid

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Animals
• Anticonvulsants (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Resistance
• Electroencephalography (drug effects)
• Epilepsy, Temporal Lobe (chemically induced, physiopathology)
• Hippocampus (drug effects, physiopathology)
• Injections
• Kainic Acid
• Male
• Mice
• Mice, Inbred Strains
• Purinergic P1 Receptor Agonists
• Receptors, Purinergic P1 (physiology)
• Temporal Lobe (drug effects, physiopathology)