Peeters Magali, Maloteaux Jean-Marie, Hermans Emmanuel
Laboratoire de Pharmacologie Expérimentale (FARL), Université Catholique de Louvain 54.10, Avenue Hippocrate 54, B-1200 Brussels, Belgium.
Neurosci Lett. 2003 Jun 12;343(3):205-9. doi: 10.1016/s0304-3940(03)00398-7.
Striatal glutamatergic inputs are known to participate in the modulation of dopaminergic transmission. Accordingly, the non-competitive N-methyl-D-aspartate receptor antagonists memantine and amantadine increase striatal dopamine levels, the latter being widely used in Parkinson's disease therapy. Based on our previous work revealing increased function of dopamine receptors and dopamine transporter after amantadine treatment, we studied the effects of repeated memantine administration on dopaminergic neurotransmission. On rat striatal membranes, dopamine-stimulated [(35)S]GTPgammaS binding was significantly reduced (20%) after 2 days injection with memantine (20 mg/kg per day, i.p.) but not after longer treatments (4 or 7 days). Evaluation of [(3)H]SCH 23390 and [(3)H]spiperone specific bindings only revealed a significant increase in D1 receptor density after 4 or 7 days treatment. Finally, none of these treatments were found to change the activity of the neuronal dopamine transporter in striatal synaptosomes. This shows that amantadine and memantine differentially affect striatal dopaminergic transmission, which could indicate that these two related aminoadamantanes display distinct pharmacodynamic properties.
已知纹状体谷氨酸能输入参与多巴胺能传递的调节。因此，非竞争性N-甲基-D-天冬氨酸受体拮抗剂美金刚和金刚烷胺可提高纹状体多巴胺水平，后者广泛用于帕金森病治疗。基于我们之前的研究揭示了金刚烷胺治疗后多巴胺受体和多巴胺转运体功能增强，我们研究了重复给予美金刚对多巴胺能神经传递的影响。在大鼠纹状体膜上，每天腹腔注射美金刚（20 mg/kg）2天后，多巴胺刺激的[(35)S]GTPγS结合显著降低（20%），但较长时间治疗（4天或7天）后则未降低。[(3)H]SCH 23390和[(3)H]螺哌隆特异性结合评估仅显示在治疗4天或7天后D1受体密度显著增加。最后，未发现这些治疗方法会改变纹状体突触体中神经元多巴胺转运体的活性。这表明金刚烷胺和美金刚对纹状体多巴胺能传递的影响不同，这可能表明这两种相关的氨基金刚烷具有不同的药效学特性。
