EFFECTS OF CE IN THE MPTP PRIMATE MODEL OF PARKINSON'S DISEASE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。大麻素系统似乎参与了与运动行为相关的基底神经节机制，因此，作用于大麻素受体的药物可能在帕金森病的治疗中发挥作用。的疾病。本研究的目的是确定和特点的影响CE，大麻素拮抗剂，运动行为特征来自帕金森？的疾病。在MPTP动物模型中，我们将研究CE对自然疾病及其慢性治疗的模拟过程中表现出的各种运动状态的具体作用。具体而言，我们将确定：1-剂量-反应曲线研究中CE的内在抗帕金森病作用，2-在交叉设计的盲法试验中通过比较不同剂量CE和左旋多巴产生的反应，确定抗帕金森病作用的大小，3-在盲法对照试验中通过两种药物联合给药，确定CE对左旋多巴作用的协同作用，和4-CE对表现出对左旋多巴的运动障碍反应的晚期帕金森病猴中左旋多巴诱导的运动障碍的作用。随后，根据先前的结果，可以包括CE与左旋多巴联合长期治疗的试验，以检查耐受性。在所有试验中，我们将通过运动残疾和不自主运动的评级来评估运动行为。这个项目即将结束。CE在与左旋多巴联合给药的试验中显示出效果。该药具有左旋多巴的抗帕金森病作用，对左旋多巴诱导的运动障碍无恶化作用。我们现在正在进行数据的最后分析和出版物的准备工作。将提交继续研究的建议，以进一步确定该药物的治疗应用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The cannabinoid system seems to be involved in basal ganglia mechanisms related to motor behavior and, thus, drugs acting on cannabinoid receptors may play a role in the therapy of Parkinson?s disease. This study aims to identify and characterize the effects of CE, a cannabinoid antagonist, on motor behavioral features derived from Parkinson?s disease. In the MPTP animal model, we will examine the specific action of CE on various motor states manifested during the mimicked course of the natural disease and its chronic treatment. Specifically, we will determine: 1-the intrinsic antiparkinsonian action of CE in a dose-response curve study, 2-the magnitude of antiparkinsonian effects by comparing responses produced by different doses of CE and levodopa in a blinded trial with crossover design, 3-the synergism of CE to the levodopa action by co-administration of both drugs in a blinded controlled trial, and 4-the effects of CE on levodopa-induced dyskinesias in advanced parkinsonian monkeys that exhibit dyskinetic responses to levodopa. Subsequently and depending on the precedent results, tests of chronic treatment of CE in combination with levodopa may be included to examine tolerance. In all trials, we will assess motor behavior with the rating of motor disability and involuntary movements. This project is near to conclusion. CE has shown effects on trials of co-administration with levodopa. The drug prolongs the antiparkinsonian action of levodopa and has no worsening effects on levodopa-induced dyskinesias. We now are working on final analysis of data and preparation of publications. Proposal for continuation of studies will be submitted to further determine therapeutic applications of this drug.