NIMODIPINE AND MEMANTINE FOR THE NEUROLOGICAL MANIFESTATIONS OF HIV-1

HIV-1的神经学表现在一到两个之间- 三分之一的成人艾滋病患者。这些并发症包括 一种痴呆症，产生认知、运动和可能的视觉 在没有病毒感染的神经元中的功能障碍 机会性双重感染，在没有艾滋病毒相关的情况下 中枢神经系统的恶性肿瘤。最近在实验室里取得了进展 对这种类型痴呆(称为艾滋病)的基础的调查 痴呆症，或最近的HIV相关运动/认知 复杂)。来自世界各地不同实验室的证据 这表明在大脑中观察到的神经元丢失的至少一部分 可能与艾滋病患者的最终共同途径有关 过度刺激兴奋性氨基酸受体，如N- 这些受体的甲基-D-天冬氨酸(NMDA)亚型。这些发现是 在当前神经科学研究的主流中，已经发现 几种急性和退行性神经疾病，从中风 对创伤和癫痫到亨廷顿病，可能有类似的基础 用于神经元损伤。面对兴奋性氨基酸的过度刺激 酸性受体，离子通道允许钙离子过度内流和 继而导致神经细胞损伤。尽管神经元的确切机制 钙超载造成的损伤仍在紧张调查中 目前的争论中，许多实验室都发现限制细菌的涌入 在这些条件下，钙离子可以保护神经元免受损伤。为 例如，使用体外和活体动物进行的实验室调查 模型表明，阻断钙离子通道可以渗透到钙离子 离子可能防止HIV感染的巨噬细胞引起的神经细胞损伤 或由HIV-1外壳蛋白gp120刺激的巨噬细胞。至少两个 离子通道的类型促成了这种形式的损伤，L型电压- 依赖性钙通道和NMDA受体偶联通道。为了这个 提出了临床可耐受的这些通道拮抗剂的原因 与现有最好的抗逆转录病毒药物一起进行研究 治疗，即齐多夫定(ZDV)或核苷，如双脱氧肌苷 (DDI)。第二项研究将用于这些抗癌药物的辅助治疗。 逆转录病毒另一种著名的药物美金刚，最近被 公认为一种有效的NMDA开放通道阻滞剂，能够 减轻暴露于gp120所致的神经元损伤 P.I.S实验室。

The neurological manifestations of HIV-1 affect between one and two- thirds of adults patients with AIDS. Included in these complications are a form of dementia producing cognitive, motor, and possible visual dysfunction in the absences of viral infection of neurons, in the absence of opportunistic superinfections, and in the absence of HIV-associated malignancies of the CNS. Recent progress has been made in the laboratory investigation of the basis for this form of dementia (termed the AIDS dementia complex, or more recently, HIV-associated motor/cognitive complex). Evidence from a variety of laboratories around the world suggests that at least part of the neuronal loss observed in the brains of patients with AIDS may be related to a final common pathway invoking excessive stimulation of excitatory amino acid receptors such as the N- methyl-D-aspartate (NMDA)subtype of these receptors. These findings are in the mainstream of current neuroscience research which has found that several acute and degenerative neurologic disorders, ranging from stroke to trauma and epilepsy to Huntington's disease, may have a similar basis for neuronal injury. In the face of overstimulation of excitatory amino acid receptors, ion channels permit excessive influx of calcium ions and consequent nerve cell injury. Although the exact mechanism for neuronal injury by calcium overload is still a matter of intense investigation and current debate, many laboratories have found that limiting the influx of calcium ions under these conditions can protect neurons form injury. For example, laboratory investigation using in vitro and in vivo animal models has suggested that blockade of ion channels permeable to calcium ions may prevent nerve cell damage engendered by HIV-infected macrophages or macrophages stimulated by the HIV-1 coat protein, gp120. At least two types of ion channels contribute to this form of injury, L-type voltage- dependent calcium channels and NMDA receptor-coupled channels. For this reason, clinically-tolerated antagonists of these channels are proposed to be studied in conjunction with the best available anti-retroviral therapy, i.e. zidovudine (ZDV) or nucleosides such as dideoxyinosine (ddI). A second study will be used an adjunctive therapy to these anti- retroviral another well-known drug, memantine, which has recently been recognized to be a potent NMDA open-channel blocker capable of attenuating neuronal injury associated with exposure to gp120 by the P.I.'s laboratory.