Effect of Pyrithioxine on the Histo-Hematic Barriers
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概要
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Pyrithioxine (pyridoxine 5-disulfide) increased the pentobarbital-induced sleeping time in mice. This potentiation was divided into two phases ; one appeared immediately after the administration of pyrithioxine and reached a maximum within 20 min. The other appeared 8-10 hr later and corresponded to the inhibition of hepatic drug-metabolizing enzymes. When the potentiation without relation to the inhibition of hepatic drug-metabolizing enzymes occurred, the pentobarbital concentration increased in the brain and liver, but was unchanged in the serum. Pyrithioxine stimulated the transport of ^<14>C-labeled fatty acids, glucose, amino acids, acetic acid, and inulin into the brain and liver, same as pentobarbital. Since [Na^++K^+]-ATPase, K^+-phosphatase, and [Mg^<2+>+Ca^<2+>]-ATPase activities were not influenced by pyrithioxine, this stimulation was not dependent on the increase of active transport, but depended on the increase of passive transport. However, the uptake of radioiodinated human serum albumin into the brain and liver of mice and the water content of these tissues were not affected by pyrithioxine treatment. The brain was not stained by Trypan Blue in pyrithioxine-treated and in control mice, but the liver, kidneys, intestines, skin, abdominal wall, and tail were stained deeper in pyrithioxine-treated mice. Increase in radioactivity from octanoate-1-^<14>C was detected only in the free fatty acid fraction in the brain, but the radioactivity in the liver increased in the free fatty acid and the triglyceride fractions. This shows that pyrithioxine affects not only the histo-hematic barrier but also the fatty acid metabolism in the liver. Brain pentobarbital concentration at the time of awakening was lower in pyrithioxine-treated mice than the control. This result suggests that pyrithioxine increases the susceptibility of central nervous system to barbiturates. In addition, increased uptake of ^<45>Ca in the brain indicates the disturbance of ion transport regulation which is necessary to preserve the central nervous excitability. These results suggest that pyrithioxine increases the pentobarbital sleeping time by three mechanisms of (1) inhibition of hepatic drug-metabolizing enzymes, (2) increase in brain pentobarbital concentration, and (3) decrease of excitability of the central nervous system.
- 公益社団法人日本薬学会の論文
- 1972-07-25
著者
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内山 充
Pharmaceutical Institute, Tohoku University
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内山 充
National Institute of Hygienic Sciences
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遠藤 賢裕
Pharmaceutical Institute Tohoku University
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Uchiyama M
Happy World Inc. Tokyo Jpn
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