PCP AND THE NMDA RECEPTOR

苯环己哌啶（PCP）是一种广泛滥用的药物（如天使粉）， 中枢神经系统的各种活动。许多 五氯苯酚引起的行为效应被认为是由阻断 兴奋性神经传递通过NMDA受体。活动 这种受体的活性对许多正常的大脑功能至关重要， 学习和记忆。然而，并非所有阻断NMDA的化合物 受体具有与PCP相同的行为效应。右美沙芬 另一种非竞争性NMDA受体拮抗剂，被认为是结合 与PCP相同的部位，但这种药物具有非常不同的 方面的影响.本项目的两个主要目标是了解 NMDA受体与非竞争性 拮抗剂，如PCP，并确定亚基组成， NMDA受体的化学计量。几个具体问题将 在项目过程中，包括：l）是否有 与PCP相互作用不同的NMDA受体亚型，2）如何 是由不同亚基组装的NMDA受体亚型，3）什么 是NMDA受体的化学计量，4）NMDA受体的哪些区域 5）NMDA受体中的哪些氨基酸是最重要的 对于药物结合重要，6）来自多种NMDA受体的氨基酸 亚基与PCP相互作用，7）所有非竞争性激动剂的 NMDA受体与NMDA受体的相同亚型结合，8）它是 开发阻止五氯苯酚结合的药物， NMDA受体通道。

Phencyclidine (PCP) is a widely abused drug (e.g. angel dust) which has a variety of actions in the central nervous system. Many of the behavioral effects induced by PCP are thought to result from the blockade of excitatory neurotransmission through the NMDA receptor. The activity of this receptor is critical for many normal brain functions including learning and memory. However, not all compounds that block the NMDA receptor have the same behavioral effects as PCP. Dextromethorphan is another non-competitive NMDA receptor antagonist that is thought to bind to the same site as PCP, but this drug has very different behavioral effects. The two major goals of this project are to understand the molecular interactions between the NMDA receptor and non-competitive antagonists like PCP and to determine the subunit composition and stoichiometry of the NMDA receptor. Several specific questions will be addressed during the course of the project including: l) are there subtypes of NMDA receptors which interact differently with PCP, 2) How are subtypes of NMDA receptors assembled from various subunits, 3) what is the stoichiometry of the NMDA receptor, 4) Which regions of the NMDA receptor bind PCP 5) Which amino acids in the NMDA receptor are most important for drug binding, 6) do amino acids from multiple NMDA receptor subunits interact with PCP, 7) do all non-competitive agonists of the NMDA receptor bind to the same subtypes of NMDA receptor, 8) is it feasible to develop drugs to block PCP binding which will not block the NMDA receptor channel.