Pentobarbital耐性の発現機序に関する研究

抄録

In rats, repeated administration of barbital was shown to cause a marked decrease in the duration of pentobarbital narcosis.
Attempts were made to examine whether the tolerance occurs as a result of a decreased sensitivity of the brain mechanism to the effects of pentobarbital or as a result of an increase in the rate of metabolism or an alteration in uptake and/or efflux of the drug by the brain tissues. In rats tolerant to pentobarbital, the rate of disappearance of the drug from the plasma or brain was more faster than that in non-tolerant rats, suggesting an increase in the metabolism of the drug. On the contrary, brain- and plasmaconcentrations of pentobarbital at the end of narcosis were significantly higher in tolerant rats than those in non-tolerant rats, suggesting the involvement of some type of neuronal adaptation referred to as cellular tolerance. Ability of the brain slices to take up ¹⁴C-pentobarbital or ¹⁴C-Aminoisobutyric acid was not affected by repeated administration of barbital to the animals.