ANTIBODY-BASED THERAPY FOR PHENCYCLIDINE 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。

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.