Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.