ANTIBODY-BASED THERAPY FOR PHENCYCLIDINE ABUSE

针对苯环利定滥用的抗体疗法

• 批准号: 2638334
• 负责人: JOEL S HARDIN
• 金额: $ 1.4万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2638334
• 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） 本课题的研究目标是研究其原理和机制， 参与苯环利定（PCP）滥用的抗体治疗。 研究 来自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 是一种类特异性拮抗剂，可有效对抗 芳基环己胺类药物，并逆转PCP诱导的毒性 剂量依赖性 此外，抗PCP Fab显著改变了 五氯苯酚的处置，并使五氯苯酚迅速重新分布， 个脑袋 接下来的一系列实验将用来检验这种疗法 在一个大型动物模型中，狗。 这些研究将检验这一假设 抗PCP Fab逆转PCP诱导的毒性， 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查抗PCP Fab 改变PCP的处置，行为研究将调查 抗PCP Fab逆转PCP诱导的毒性。 雄性和雌性犬 将被用于这些研究，以确定是否有任何狗的性别 治疗的差异。 合并药代动力学/ 将使用大鼠和犬的药效学模型来扩大治疗 对人类 因此，这些数据应提供重要的信息， 开发针对其他滥用药物的抗体疗法。