BEHAVIORAL PHARMACOLOGY OF PCP & RELATED COMPOUNDS

五氯苯酚的行为药理学

• 批准号: 3211605
• 负责人: james H Woods
• 金额: $ 22.28万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3211605
• 关键词: Alzheimer's disease; Macaca mulatta; NMDA receptors; PCP receptor; behavior test; catalepsy; diagnosis design /evaluation; discrimination learning; excitatory aminoacid; ketamine; laboratory rat; memory disorders; neurotransmitters; phencyclidine; pigeons; psychopharmacology; psychotomimetic drug

This proposal is designed to evaluate the behavioral effects of antagonists of N-methyl-D-aspartate, and compare these effects to those of PCP and related compounds. Among the PCP-specific assays that will be used are PCP discrimination and catalepsy in the pigeon and ketamine discrimination in the monkey. Identification of behiaviors in the rat related to binding at the newly discovered signma receptor is the second goal of this proposal. These data may produce new leads for treatment of psychosis. Finally, procedures that may assist in measuring memory disturbances related to pharmacologically-induced Alzheimer's disease are proposed. The effects of excitatory amino acids and their antagonists will be evaluated in this procedure. These studies are predicated on recent reports of an inhibitory effect of PCP and ketamine on excitatory amino acid neurotransmission , and the finding of a novel binding site for psychotomimetic opiates. These findings have produced tremendous excitement about new drug development and the possibility of further understanding about the mechanism of action of PCP and related compounds. Because PCP is subject to abuse, produces signs similar to those of schizophrenia, is a prototype for a novel anesthetic, and has anticonvulsant activity, it is of considerable interest to evaluate its mechanism closely. Data that indicate that excitatory amino acids have neurotoxic effects, including the possibility of a relationship to Alzheimer's disease, increase interest in antagonists of excitatory amino acid actions. Most of the excitement about PCP has been generated by biochemical and electrophysiological work. It is essential that careful behavior studies be undertaken using the new drugs that have been recently synthesized or identified as being related to excitatory amino acid transmission. Behavioral data will permit a more rational integration of information coming from other in vivo and in vitro procedures.

该提案旨在评估行为影响 N-甲基-D-天冬氨酸拮抗剂，并比较这些效果 五氯酚 (PCP) 及相关化合物的含量。 PCP 特定的 将使用的测定是 PCP 歧视和僵住症 猴子身上的鸽子和氯胺酮歧视。 大鼠中与结合相关的行为的鉴定 新发现的signma受体是该研究的第二个目标 提议。 这些数据可能会产生新的治疗线索 精神病。 最后，可能有助于测量的程序 与药物引起的记忆障碍有关 提出了阿尔茨海默病。 兴奋性的影响 氨基酸及其拮抗剂将在此进行评估 程序。 这些研究基于最近的抑制性报告 五氯苯酚和氯胺酮对兴奋性氨基酸的影响 神经传递，以及新的结合位点的发现 拟精神病阿片类药物。 这些发现产生了 对新药开发和 进一步了解其机制的可能性 五氯苯酚和相关化合物的作用。 因为 PCP 受 滥用，产生类似于精神分裂症的症状，是一种 一种新型麻醉剂的原型，并具有抗惊厥活性， 仔细评估其机制具有相当大的意义。 数据表明兴奋性氨基酸具有神经毒性 影响，包括与阿尔茨海默病有关的可能性 疾病，增加对兴奋性氨基酸拮抗剂的兴趣 行动。 关于 PCP 的大部分兴奋已经产生 通过生化和电生理工作。 至关重要的是 使用新药物进行仔细的行为研究 最近被合成或鉴定为与 兴奋性氨基酸传递。 行为数据将允许 更合理地整合来自其他领域的信息 体内和体外程序。