Chen L S, Millington D S, Maltby D A, McNamara J O
Department of Pharmacology and Medicine (Neurology), Duke University Medical Center, Durham, North Carolina.
Neuropharmacology. 1989 Aug;28(8):781-6. doi: 10.1016/0028-3908(89)90167-6.
The authors sought to determine whether focal application of clinically-effective anticonvulsants to the substantia nigra produced anticonvulsant effects. To this end, the effects of phenobarbital, carbamazepine and phenytoin were examined on the electroshock seizure model in rats. Anticonvulsant efficacy was assessed by measuring the duration of tonic hindlimb extension before and after injection. It was found that application of phenobarbital into the nigra produced behavioral stereotypy and suppressed tonic hindlimb extension in a dose-dependent manner. These effects were spatially specific to the substantia nigra. By contrast, application of phenytoin or carbamazepine to the nigra produced neither anticonvulsant effects nor behavioral changes. Direct measurement of phenobarbital and carbamazepine in the substantia nigra showed that differences in concentration in the substantia nigra did not account for the lack of efficacy of carbamazepine. Moreover, concentrations of phenobarbital in the nigra after effective injection into the nigra exceeded concentrations in the nigra after effective systemic injections, by tenfold. Taken together, these data provide no compelling evidence that an action of the substantia nigra alone is sufficient to explain the therapeutic action of clinically-useful anticonvulsants.
作者试图确定将临床有效的抗惊厥药物局部应用于黑质是否会产生抗惊厥作用。为此，研究了苯巴比妥、卡马西平和苯妥英对大鼠电休克惊厥模型的影响。通过测量注射前后强直性后肢伸展的持续时间来评估抗惊厥疗效。结果发现，将苯巴比妥注入黑质会产生行为刻板症，并以剂量依赖的方式抑制强直性后肢伸展。这些作用在空间上对黑质具有特异性。相比之下，将苯妥英或卡马西平应用于黑质既不产生抗惊厥作用，也不引起行为变化。对黑质中苯巴比妥和卡马西平的直接测量表明，黑质中浓度的差异并不能解释卡马西平缺乏疗效的原因。此外，有效注入黑质后黑质中苯巴比妥的浓度比有效全身注射后黑质中的浓度高出十倍。综上所述，这些数据没有提供令人信服的证据表明仅黑质的作用就足以解释临床有用的抗惊厥药物的治疗作用。
