Peeters B W, Ramakers G M, Vossen J M, Coenen A M
Department of Neuropharmacology, Organon International B. V., Oss, The Netherlands.
Brain Res Bull. 1994;33(6):709-13. doi: 10.1016/0361-9230(94)90236-4.
The involvement of AMPA and kainate receptors in nonconvulsive epilepsy was studied by intracerebroventricular injections of AMPA, GDEE, kainic acid and kynurenic acid in WAG/Rij rats. The WAG/Rij rat strain is recognized as an animal model for human absence epilepsy. EEG registrations showed that AMPA (0.1 pmol/5 microliters; 1 pmol/5 microliters; 10 pmol/5 microliters) dose-dependently increased the nonconvulsive absence epilepsy while GDEE (0.2 mumol/5 microliters; 1 mumol/5 microliters; 5 umol/5 microliters) caused a dose-dependent decrease. All effects of GDEE could be blocked by an inactive AMPA dosage. Kainic acid (0.01 nmol/5 microliters; 0.1 nmol/5 microliters; 0.15 nmol/5 microliters) had no effects on the nonconvulsive epilepsy but induced convulsions in the two highest dosages. Kynurenic acid (50 nmol/5 microliters; 100 nmol/5 microliters; 500 nmol/5 microliters) decreased dose-dependently the incidence of nonconvulsive epilepsy. The effect of kynurenic acid could be blocked by a nonconvulsive dosage of kainic acid. These results show that the AMPA and kainate receptor appear to be involved in nonconvulsive epilepsy. Furthermore, blockage of these two receptor subtypes led to an antiepileptic effect without inducing behavioural alterations. Therefore, selective AMPA and kainate receptor antagonists might be potent anti-epileptics.
通过向WAG/Rij大鼠脑室内注射AMPA、GDEE、 kainic酸和犬尿喹啉酸，研究了AMPA和海人酸受体在非惊厥性癫痫中的作用。WAG/Rij大鼠品系被认为是人类失神癫痫的动物模型。脑电图记录显示，AMPA（0.1皮摩尔/5微升；1皮摩尔/5微升；10皮摩尔/5微升）剂量依赖性地增加非惊厥性失神癫痫，而GDEE（0.2微摩尔/5微升；1微摩尔/5微升；5微摩尔/5微升）则导致剂量依赖性降低。GDEE的所有作用都可被无活性的AMPA剂量阻断。海人酸（0.01纳摩尔/5微升；0.1纳摩尔/5微升；0.15纳摩尔/5微升）对非惊厥性癫痫无影响，但在两个最高剂量时诱发惊厥。犬尿喹啉酸（50纳摩尔/5微升；100纳摩尔/5微升；500纳摩尔/5微升）剂量依赖性地降低非惊厥性癫痫的发生率。犬尿喹啉酸的作用可被非惊厥剂量的海人酸阻断。这些结果表明，AMPA和海人酸受体似乎参与了非惊厥性癫痫。此外，阻断这两种受体亚型可产生抗癫痫作用而不引起行为改变。因此，选择性AMPA和海人酸受体拮抗剂可能是有效的抗癫痫药物。
