Effect of acetazolamide on the anticonvulsant potency of phenobarbital in mice

Effect of acetazolamide (AZA) on the anticonvulsant potency of phenobarbital (PHB) was investigated in mice by maximal electroshock seizure (MES) test. By coadministration with AZA, a remarkable increase an prolongation of the anticonvulsant activity of PHB was brought about. The type of the synergism of PHB with AZA was not additive but of potentiation. The potentiation of the anticonvulsant activity of PHB with AZA was rather related to inhibition of carbonic anhydrase (CA) in brain than in blood. The anticonvulsant activity of PHB was also increased by coadministration with methazolamide which had a great ability to inhibit brain CA. Furosemide, which had no inhibitory effect on brain CA, on the other hand, failed to show any potentiation on the anticonvulsant activity of PHB. Thus it was inferred that the inhibition of brain CA may play a significant role for the potentiation of the anticonvulsant activity of PHB. Although reserpinization completely abolished the protective effect of AZA on MES, the potentiation of the anticonvulsant activity of PHB was still observed by AZA. These results suggest that pharmacodynamic and/or pharmacokinetic effect of AZA independent of its anticonvulsant action may contribute to the potentiation of the PHB action.