Lee Jinny Claire, Janda Kim D
Department of Chemistry, Department of Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, The WIRM Institute for Research & Medicine, The Scripps Research Institute 10550 North Torrey Pines Rd La Jolla CA 92037 USA
RSC Chem Biol. 2020 Oct 8;2(1):77-93. doi: 10.1039/d0cb00165a. eCollection 2021 Feb 1.
Methamphetamine (METH) is an illicit psychostimulant that is known to account for substance abuse disorders globally, second only to opioids, yet has no approved pharmacotherapies. Traditional therapies employ small molecule agonists or antagonists for substance use disorders or overdose reversal by targeting drug-specific receptors in the brain. However, the comprehensive mechanism of METH on multiple sites within the central nervous system (CNS) implies its receptors lack the high affinity and specificity required for an "ideal" drug target. The alternative to pharmacotherapies is to sequester abused drugs in the periphery, effectively eliminating the effects from CNS receptor occupation through pharmacokinetic antagonism. This review presents updates on immunopharmacotherapeutic advancements in addressing methamphetamine abuse by focusing on the cultivation of research optimization strategies regarding hapten chemistry, carrier proteins, and adjuvants implemented in active immunization. Furthermore, we discuss necessary developments for each component of active immunopharmacotherapies and the future of active vaccines in treating METH use disorder.
甲基苯丙胺(METH)是一种非法精神兴奋剂,已知在全球范围内导致药物滥用障碍,仅次于阿片类药物,但尚无获批的药物疗法。传统疗法通过靶向大脑中的药物特异性受体,使用小分子激动剂或拮抗剂来治疗药物使用障碍或逆转药物过量。然而,METH在中枢神经系统(CNS)多个部位的综合作用机制表明,其受体缺乏“理想”药物靶点所需的高亲和力和特异性。药物疗法的替代方法是在外周隔离滥用药物,通过药代动力学拮抗作用有效消除中枢神经系统受体占据所产生的影响。本综述通过关注主动免疫中关于半抗原化学、载体蛋白和佐剂的研究优化策略的培养,介绍了免疫药物治疗在解决甲基苯丙胺滥用方面的进展。此外,我们还讨论了主动免疫药物治疗各组成部分的必要发展以及主动疫苗在治疗甲基苯丙胺使用障碍方面的未来。