左旋多巴(L-Dopa)对实验性癲痫影响的研究
INVESTIGATIONS ON THE INFLUENCE OF L-DOPA ON EXPERIMENTAL EPILEPSY
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摘要: L-Dopa对大鼠听源性发作和小鼠电休克惊厥均有明显对抗作用,但对后者的对抗作用较弱。L-Dopa的这种作用,主要与其增加脑内DA水平有关,因其作用与升高脑内DA水平相平行,脑室内直接注射DA或以去水吗啡激动DA-受体均有抗惊厥作用,而以氟哌啶阻断DA-受体,则减弱或对抗L-Dopa的作用。L-Dopa也升高脑内NE含量,对上述两种惊厥也有一定影响,但不如DA重要,至少对于大鼠听源性发作是如此。因为以双硫醒阻断NE合成,减少其脑内含量,但不能对抗大鼠听源性发作,双硫醒与L-Dopa合用,有协同作用,同样,脑室注射NE或用双羟苯丝氨酸增加大鼠脑内NE含量,对大鼠听源性发作影响不大,但α-阻断剂能减弱L-Dopa的作用。L-Dopa可作为一种治疗癫痫的辅助药物,用于DA明显减少的病例可能有益。Abstract: Investigations were carried out on the influence of L-Dopa on experimental epilepsy. L-Dopa was found to be able to markedly antagonize electroshock seizures in mice and audiogenic seizures (AGS) in rats. These effects of L-Dopa are mainly related to an increase of the concentration of dopamine (DA)in the whole brain of animals: 1). The antiaudiogenic seizure effects of L-Dopa was shown to be parallel with the incerase of the whole brain DA content, 2). Apomorphin, an agonist of dopaminergic receptor (DAR), also antagonized AGS in rats, Droperidol, an antagonist of DAR, in contrast, markedly reduced the anticonvulsant effect of L-Dopa, 3). The combined treatment with L-Dopa and disulfiram markedly reduced the whole brain NE content by 38% and signficantly increased the DA content. The anti-convulsant effects of L-Dopa was not altered. Treatment with disulfiram alone also markedly antagonized the AGS in rats(P<0.01),4). An intracerebroventricular injection of dihydroxyphenylserine (Dops) to rats, increased the whole brain NE content by 42%, the DA content, however, did not undergo any change. The susceptibility to AGS was not affected. All these results indicate that DA is more important than NE in the modulation of AGS.
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