Pharmacological inhibition of brain carbonic anhydrase protects against 4-aminopyridine seizures.

The effects of the inhibition of carbonic anhydrase on the manifestation of tonic-clonic seizures were investigated in freely-moving rats. 4-Aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult male rats with 20 or 40 mg/kg acetazolamide, 3, 5, 7 or 9 mg/kg 4-aminopyridine was injected intraperitoneally and the latencies of the symptoms were measured. Pharmacological inhibition of brain carbonic anhydrase significantly increased the latency of onset of seizures. Bolus administration of acetazolamide decreased the incidence of generalized convulsions and protected against status epilepticus. Chronic acetazolamide treatment for 2 days affected only the generalized convulsions. The results suggested that alterations of the extracellular and intracellular pH by acetazolamide decreased the efficacy of synaptic transmission in several areas of the brain. The possible effects of the HCO3- ions on the sensitivity of synaptic and nonsynaptic neuronal receptors are discussed.