ANTIBODY-BASED THERAPY FOR PHENCYCLIDINE ABUSE

针对苯环利定滥用的抗体疗法

• 批准号: 2897780
• 负责人: JOEL S HARDIN
• 金额: $ 2.6万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2897780
• 关键词: dogs; drug abuse therapy; gender difference; immunotherapy; laboratory rat; monoclonal antibody; nonhuman therapy evaluation; pharmacokinetics; phencyclidine

DESCRIPTION: (Applicant's Abstract) The goal of this research project is to study the principles and mechanisms involved in antibody-based therapy for phencyclidine (PCP) abuse. Studies from this laboratory have shown that a murine monoclinal anti-PCP Fab antibody fragment (anti-PCP Fab) is capable of reversing PCP-induced behavioral effects in rats. These studies demonstrate that the anti-PCP Fab is a class-specific antagonist that is effective against several members of the arylcyclohexylamine drug class and that it reverses PCP-induced toxicity in a dose-dependent manner. Also, the anti-PCP Fab dramatically alters the disposition of PCP and produces a rapid redistribution of PCP out of the brain. The next series of experiments will be used to examine the therapy in a large animal model, the dog. These studies will test the hypothesis that the anti-PCP Fab reverses PCP-induced toxicity in a manner that can be predicted by a pharmacokinetic/pharmacodynamic model. Consequently, the pharmacokinetic studies will examine the ability of the anti-PCP Fab to alter the disposition of PCP, and the behavioral studies will investigate the anti-PCP Fab reversal of PCP-induced toxicity. Male and female dogs will be used in these studies to determine if there are any canine sex differences in therapy. Data from the combined pharmacokinetic/ pharmacodynamic models in rats and dogs will be used to scale-up the therapy to humans. Therefore, the data should provide important information for the development of antibody-based therapy for other drugs of abuse.

描述：（申请人摘要） 该研究项目的目标是研究其原理和机制 参与针对苯环己哌啶 (PCP) 滥用的抗体疗法。 研究 该实验室的研究表明，鼠单斜抗 PCP Fab 抗体片段（抗 PCP Fab）能够逆转 PCP 诱导的 对大鼠的行为影响。 这些研究表明，抗 PCP Fab 是一种特定类别的拮抗剂，可有效对抗多种成员 芳基环己胺药物类别，它可以逆转五氯苯酚引起的毒性 以剂量依赖性方式。 此外，抗 PCP Fab 极大地改变了 五氯苯酚的处置并产生五氯苯酚的快速重新分配 脑。 下一系列实验将用于检验该疗法 在大型动物模型中，狗。 这些研究将检验假设 抗 PCP Fab 以一种可以逆转 PCP 诱导的毒性的方式 通过药代动力学/药效学模型预测。 因此， 药代动力学研究将检验抗 PCP Fab 的能力 改变 PCP 的性格，行为研究将调查 抗 PCP Fab 逆转 PCP 诱导的毒性。 雄性和雌性狗 将在这些研究中用于确定是否存在犬类性别 治疗上的差异。 数据来自组合药代动力学/ 大鼠和狗的药效学模型将用于扩大治疗规模 对人类。 因此，这些数据应该为我们提供重要的信息。 开发针对其他滥用药物的基于抗体的疗法。