Effect of Acetazolamide on Barbiturate-induced Sleeping Time in Mice. II. Effect on Barbiturate Levels in the Plasma and Brain

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In the previous paper, acetazolamide (AZA) was reported to shorten the hexobaribital sleeping time, while prolonging the norhexobarbital (NHB) sleeping time in mice. Since AZA was found to prolong the sleeping time induced with metharbital (MET) and mephobarbital (MB) as well as barbital (BA) and phenobarbital (PHB) in this study, N-methylation of barbiturates does not appear to be a critical factor in the action of AZA. The induction times of the five barbiturates, including NHB, were shortened by AZA pretreatment. At the moment of awakening from sleep, the brain level of BA was the same as that without the AZA pretreatment, which suggests unchanged brain sensitivity to the barbiturate. At that time, however, the plasma level was reduced in the case of AZA pretreatment. Similar results were obtained with PHB, MET, and MB. Thus, the prolongation of barbiturate sleep and shortening of the induction time are probably due to a decrease in the rate of removal of the barbiturates from the brain due to the reduction of cerebrospinal fluid flow and/or the inhibition of a system for acid transport out of the brain.
公益社団法人日本薬学会の論文
1980-02-25