Role of endogenous adenosine in recurrent generalized seizures.

We induced generalized seizures by cortical injection of penicillin in anesthetized, paralyzed cats. After they had developed recurrent ictal-interictal ECoG cycling and fictive tonic-clonic motor convulsions (status epilepticus), we studied the effect of systemically administered neuropharmacological agents on the seizure cycling. Antagonists of adenosine receptors, theophylline and 8-cyclopentyltheophylline, increased the cycle period due to marked prolongation of duration of ictal discharge, often to more than 30 min. Dipyridamole, an inhibitor of adenosine reuptake, lengthened the interictal phase of the seizure with no effect on ictal duration. Antagonists of gamma-aminobutyric acid and opioid peptides had no effect on either ictal or interictal phases nor did the nonspecific neural excitant, doxapram. These findings suggest that a major mechanism of ictal-interictal cycling during status epilepticus is the alternating accumulation during the ictal phase and clearance during the interictal phase of the inhibitory neurochemical, adenosine.