Elshanskaia M V, Sobolevskiĭ A I, Val'dman E A, Khodorov B I
Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315 Russia.
Eksp Klin Farmakol. 2001 Jan-Feb;64(1):18-21.
Interaction of a new potential antiparkinsonian drug, N-(2-adamantyl)hexamethyleneimine hydrochloride (A-7), with NMDA channels in acutely isolated rat hippocampal neuron culture was studied by the whole-cell patch-clamp technique. The currents through the NMDA channels were excited by aspartate (Asp) application in a magnesium-free glycine-containing (3 microM) medium. It was found that A-7 produced a concentration-dependent (IC50 = 11.8 +/- 0.6 microM) NMDA channel blocking. The blocking rate increased with the A-7 concentration, whereas the unblocking was concentration-independent. The degree of blocking was independent of the Asp concentration, but was markedly increased by hyperpolarization of the cell membrane. After Asp washout, A-7 remained trapped in the channel by the activation gate. The channel was unblocked upon the next Asp application. These data is evidence that the antiparkinsonian effect of A-7 is related to the NMDA-channel-blocking activity of the drug.
采用全细胞膜片钳技术，研究了一种新型潜在抗帕金森病药物盐酸N-(2-金刚烷基)六亚甲基亚胺(A-7)与急性分离的大鼠海马神经元培养物中NMDA通道的相互作用。在不含镁但含甘氨酸(3 microM)的培养基中，通过施加天冬氨酸(Asp)来激发通过NMDA通道的电流。结果发现，A-7对NMDA通道产生浓度依赖性阻断(IC50 = 11.8 +/- 0.6 microM)。阻断率随A-7浓度增加而升高，而解除阻断则与浓度无关。阻断程度与Asp浓度无关，但细胞膜超极化可使其显著增加。Asp洗脱后，A-7被激活门滞留在通道中。再次施加Asp时通道被解除阻断。这些数据证明A-7的抗帕金森病作用与该药物的NMDA通道阻断活性有关。
