Bourgeois B F, Dodson W E, Ferrendelli J A
Neurology. 1983 Mar;33(3):291-5. doi: 10.1212/wnl.33.3.291.
Neurotoxicity and protection against maximal electroshock (MES) and pentylenetrazol (Metrazol) seizures were determined in mice for various combinations of primidone (PRM), phenobarbital (PB), and phenylethylmalonamide (PEMA). The results suggest that PRM and PB together are superior to either one alone in terms of spectrum of activity and relative toxicity. The protection against Metrazol and the toxicity of PB are both potentiated by PEMA at low concentrations. PEMA also potentiates the toxicity of combined PRM plus PB, without altering their protection against MES, thus lowering their therapeutic index. We conclude that PRM and PB together have an advantage over PB alone, especially when their brain concentration ratio is at or above 1 and PEMA concentrations are low. These conditions are usually not present at steady state in patients treated with PRM.
在小鼠中测定了扑米酮（PRM）、苯巴比妥（PB）和苯乙基丙二酰胺（PEMA）的各种组合的神经毒性以及对最大电休克（MES）和戊四氮（Metrazol）惊厥的保护作用。结果表明，就活性谱和相对毒性而言，PRM和PB联合使用优于单独使用任何一种。低浓度的PEMA可增强对Metrazol的保护作用以及PB的毒性。PEMA还可增强PRM加PB联合使用的毒性，但不改变它们对MES的保护作用，从而降低它们的治疗指数。我们得出结论，PRM和PB联合使用比单独使用PB具有优势，尤其是当它们的脑浓度比等于或高于1且PEMA浓度较低时。在用PRM治疗的患者中，这些情况在稳态时通常不存在。
