Schmidt D, Kupferberg H J, Yonekawa W, Penry J K
Epilepsia. 1980 Apr;21(2):141-7. doi: 10.1111/j.1528-1157.1980.tb04055.x.
The development of tolerance to the anticonvulsant effect of chronically administered phenobarbital was demonstrated in mice by the maximal electroshock (MES) test. Anticonvulsant activity decreased 50% over a 5 day period. Brain and plasma levels of phenobarbital measured 2 hr after a 25 mg/kg dose of phenobarbital were the same between days 1 and 5, indicating that distributional or pharmacokinetic parameters were not involved. The loss of anticonvulsant activity of phenobarbital is primarily related to the drug's effect to prevent the spread of MES-induced epileptic neuronal activity. In contrast, the anticonvulsant action of phenobarbital on seizure threshold, as measured by the minimal electroshock seizure threshold (EST) test, and on the spread of epileptic discharge induced by pentylenetetrazol (PTZ), as evaluated by the PTZ infusion test, remained unchanged.
通过最大电休克（MES）试验证明，长期给予苯巴比妥后，小鼠对其抗惊厥作用产生了耐受性。在5天的时间里，抗惊厥活性降低了50%。在第1天和第5天，给予25mg/kg剂量的苯巴比妥2小时后，大脑和血浆中的苯巴比妥水平相同，这表明分布或药代动力学参数未参与其中。苯巴比妥抗惊厥活性的丧失主要与该药物阻止MES诱导的癫痫神经元活动扩散的作用有关。相比之下，通过最小电休克惊厥阈值（EST）试验测量，苯巴比妥对惊厥阈值的抗惊厥作用，以及通过戊四氮（PTZ）输注试验评估，其对PTZ诱导的癫痫放电扩散的抗惊厥作用保持不变。
