论文标题
抗组胺药的当前状态重新利用感染性疾病
Current status of antihistamines repurposing for infectious diseases
论文作者
论文摘要
目标。这篇综述收集了有关抗组胺药作为抗感染剂的潜在作用的信息，并确定了损害其在人类健康中适用性的研究中的差距。方法。 1990年至2022年，文献搜索涵盖了Medline，PubMed和Google Scholar。结果。文献搜索确定了12种抗组胺药，其活性对不同的病原体。八个分子是第二代抗组胺药，其本质上较低的趋势越过血脑屏障，从而减少了副作用。只有五个抗组胺药在啮齿动物中进行体内评估，而一项研究利用蜡像蛾模型来确定astemizole抗晶状体SP。活性与氟康唑结合。体外研究表明，轻质素对疟原虫，利什曼原虫和锥虫瘤具有活性，而Terfenadine抑制了念珠菌属。和金黄色葡萄球菌的生长。体外测定法发现SARS-COV-2被Doxepin，Azelastine，Desloratadine和Clemastine抑制。不同的抗组胺药抑制埃博拉病毒（二苯胺，氯环嗪），丙型肝炎病毒（氯环辛）和流感病毒（甲氧胺，氯苯胺）。通常，抗组胺药的体外活性（IC50）在低至亚微米范围内，除了表皮葡萄球菌（Loratadine MIC = 50 microm）和SARS-COV-2（Desloratine 70％抑制在20 microm时）除外。结论。许多抗组胺药在基于体外数据以及毒理学和药理数据的可用性方面表现出了进展到临床试验的潜力。然而，总体缺乏系统的临床前试验阻碍了重新利用的抗组胺药进行关闭标签评估的进步。制药公司的低兴趣必须通过研究小组之间的合作来抵消平衡，授予机构和政府支持所需的临床试验。
Objectives. This review gathers information on the potential role of antihistamines as anti-infective agents and identifies gaps in research that have impaired its applicability in human health. Methods. The literature search encompassed MEDLINE, PubMed and Google Scholar from 1990 to 2022. Results. The literature search identified 12 antihistamines with activity against different pathogens. Eight molecules were second-generation antihistamines with intrinsically lower tendency to cross the blood brain barrier thereby with reduced side effects. Only five antihistamines had in vivo evaluations in rodents while one study utilized a wax moth model to determine astemizole anti-Cryptococcus sp. activity combined with fluconazole. In vitro studies showed that clemastine was active against Plasmodium, Leishmania, and Trypanosoma, while terfenadine suppressed Candida spp. and Staphylococcus aureus growth. In vitro assays found that SARS-coV-2 was inhibited by doxepin, azelastine, desloratadine, and clemastine. Different antihistamines inhibited Ebola virus (diphenhydramine, chlorcyclizine), Hepatitis C virus (chlorcyclizine), and Influenza virus (carbinoxamine, chlorpheniramine). Generally, in vitro activity (IC50) of antihistamines was in the low to sub-microM range, except for Staphylococcus epidermidis (loratadine MIC=50 microM) and SARS-coV-2 (desloratadine 70% inhibition at 20 microM). Conclusion. Many antihistamine drugs showed potential to progress to clinical trials based on in vitro data and availability of toxicological and pharmacological data. However, the overall lack of systematic preclinical trials has hampered the advance of repurposed antihistamines for off label evaluation. The low interest of pharmaceutical companies has to be counterbalanced through collaborations between research groups, granting agencies and government to support the needed clinical trials.
