Deupree J D, Downs D A, Laposky J E, Hitchcock J J
J Pharmacol Exp Ther. 1984 Jul;230(1):171-4.
The anticonvulsant drug, phenytoin, has been reported to inhibit both the transport of catecholamines into synaptosomes and monoamine oxidase. The objective of this research was to determine whether phenytoin inhibited the transport of catecholamines into storage granules. This was tested by examining the effects of phenytoin (0.05 to 0.4 mM) on the ability of (-)-[3H] norepinephrine to be transported into chromaffin granule "ghosts" isolated from bovine adrenal glands. Our results indicated that phenytoin, but not phenobarbital, inhibited catecholamine transport in a dose-dependent manner with 50% inhibition occurring at a phenytoin concentration of 0.2 mM. Kinetic analysis of the effects of phenytoin on this transport process indicated that phenytoin was a competitive inhibitor of catecholamine transport with an approximate Ki of 0.3 mM. Furthermore, phenytoin did not inhibit the Mg adenosine triphosphatase required for providing the energy source for the catecholamine transport process, nor did it dissipate the membrane potential generated by this enzyme. The competitive inhibition of catecholamine transport produced by phenytoin is probably not related to the anticonvulsant effects of the drug as it occurred at greater than therapeutic concentrations. However, this effect may be related to the toxic effect of the drug.
据报道，抗惊厥药物苯妥英可抑制儿茶酚胺向突触小体的转运以及单胺氧化酶的活性。本研究的目的是确定苯妥英是否抑制儿茶酚胺向储存颗粒的转运。通过检测苯妥英（0.05至0.4 mM）对（-）-[3H]去甲肾上腺素转运至从牛肾上腺分离的嗜铬颗粒“空壳”能力的影响来进行测试。我们的结果表明，苯妥英而非苯巴比妥以剂量依赖方式抑制儿茶酚胺转运，在苯妥英浓度为0.2 mM时出现50%的抑制。对苯妥英对该转运过程影响的动力学分析表明，苯妥英是儿茶酚胺转运的竞争性抑制剂，其近似Ki为0.3 mM。此外，苯妥英不抑制为儿茶酚胺转运过程提供能量来源所需的镁三磷酸腺苷酶，也不消除该酶产生的膜电位。苯妥英对儿茶酚胺转运的竞争性抑制可能与该药物的抗惊厥作用无关，因为这种抑制发生在高于治疗浓度时。然而，这种作用可能与该药物的毒性作用有关。
