Ochoa-Aguilar Abraham, Ventura-Martinez Rosa, Sotomayor-Sobrino Marco Antonio, Gómez Claudia, Morales-Espinoza María del Rosario
Departamento de Farmacología. Facultad de Medicina. Universidad Nacional Autonoma de Mexico Av. Universidad No. 3000, Col. Ciudad Universitaria. Delegación Coyoacán. C.P. 04510, México, D.F, Mexico.
Antiinflamm Antiallergy Agents Med Chem. 2016;15(1):3-14. doi: 10.2174/1871523015666160517114027.
Beta-lactam molecules are a family of drugs commonly used for their antibiotic properties; however, recent research has shown that several members of this group present a large number of other effects such as neuroprotective, antioxidant, analgesic or immunomodulatory capabilities. These properties have been used in both preclinical and clinical studies in different diseases such as hypoxic neuronal damage or acute and chronic pain. The present work briefly reviews the antibiotic effect of these molecules, and will then focus specially on the non-antibiotic effects of three beta-lactam subfamilies: penicillins, cephalosporins and beta lactamase inhibitors, each of which have different molecular structure and pharmacokinetics and therefore have several potential clinical applications.
A thorough search of bibliographic databases for peer-reviewed research was performed including only classic experiments or high quality reviews for the antibiotic mechanisms of beta-lactam molecules and only experimental research papers where included when the non-antibiotic properties of these molecules were searched. Only published articles from indexed journals were included. Quality of retrieved papers was assessed using standard tools. The characteristics of screened papers were described and findings of included studies were contextualized to either a mechanistic or a clinical framework.
Seventy-eight papers were included in the review; the majority (56) were relative to the non-antibiotic properties of beta-lactam molecules. The non-antibiotic effects reviewed were divided accordingly to the amount of information available for each one. Twelve papers outlined the epileptogenic effects induced by beta-lactam molecules administration; these included both clinical and basic research as well as probable mechanistic explanations. Eighteen papers described a potential neuroprotective effect, mostly in basic in vitro and in vivo experiments. Analgesic properties where identified in twelve papers and basic research was described alongside with both experimental and serendipic clinical findings. Seven papers described a down-regulation effect exerted by beta-lactam molecules administration in different addiction animal models. Finally other effects such as penile erection, dopamine release facilitation and anti-neoplasic effects where described from seven papers.
The findings of this review show that beta-lactam molecules may induce several effects, which may be clinically relevant in a lot of different diseases. This paper is, to our knowledge, the first comprehensive review of the non-antibiotic effects shown by beta-lactam molecules and may help increase the interest in this field, which may result in a direct translation of this effects to a clinical context.
β-内酰胺类分子是一类因其抗生素特性而常用的药物；然而，最近的研究表明，该类药物中的几种还具有大量其他作用，如神经保护、抗氧化、镇痛或免疫调节能力。这些特性已在缺氧性神经元损伤或急慢性疼痛等不同疾病的临床前和临床研究中得到应用。本研究简要回顾了这些分子的抗生素作用，然后将特别关注三个β-内酰胺亚家族（青霉素类、头孢菌素类和β-内酰胺酶抑制剂）的非抗生素作用，它们各自具有不同的分子结构和药代动力学，因此有多种潜在的临床应用。
对文献数据库进行全面检索，以查找同行评审的研究，仅纳入关于β-内酰胺类分子抗生素机制的经典实验或高质量综述，在查找这些分子的非抗生素特性时仅纳入实验研究论文。仅纳入索引期刊上发表的文章。使用标准工具评估检索到的论文质量。描述筛选论文的特征，并将纳入研究的结果置于机制或临床框架中。
该综述纳入了78篇论文；其中大多数（56篇）与β-内酰胺类分子的非抗生素特性有关。所综述的非抗生素作用根据每种作用可得的信息量进行了分类。12篇论文概述了β-内酰胺类分子给药诱导的致痫作用；这些论文包括临床和基础研究以及可能的机制解释。18篇论文描述了潜在的神经保护作用，主要是在基础体外和体内实验中。12篇论文确定了镇痛特性，并描述了基础研究以及实验性和意外的临床发现。7篇论文描述了β-内酰胺类分子给药在不同成瘾动物模型中产生的下调作用。最后，7篇论文描述了其他作用，如阴茎勃起、多巴胺释放促进和抗肿瘤作用。
本综述的结果表明，β-内酰胺类分子可能会产生多种作用，这些作用在许多不同疾病中可能具有临床相关性。据我们所知，本文是对β-内酰胺类分子所显示的非抗生素作用的首次全面综述，可能有助于提高该领域的关注度，这可能会使这些作用直接转化到临床应用中。
