Old Drugs: Confronting Recent Advancements and Challenges

Over the years, there has been an increasing demand for an effective and cost-efficient drug discovery process. The study of old and previously-approved drugs for newer indications or their re-evaluation based on newly-identified different mechanisms of action has become a major focus of drug discovery, particularly when it comes to treating chronic or complex multigenetic diseases such as cancer, autoimmune, neurodegenerative disorders, and psychiatric conditions. This approach is actually particularly appealing since it saves time and resources and reduces the risk of failure. The history of pharmacology is replete with examples of drugs that have undergone significant shifts in their clinical or preventive use over time, such as acetylsalicylic acid, thalidomide, duloxetine, and dapagliflozin. For instance, acetylsalicylic acid has been used for over a century as an anti-inflammatory and analgesic, but it is currently used as an antiplatelet agent. Thalidomide was previously removed from the market because of its teratogenic effects which were associated with the inhibition of the synthesis of tumor necrosis factor-alpha and other cytokines, but it has since emerged as an immunomodulator for the treatment of various diseases, including erythema nodosum leprosum. Intriguingly, repurposed drugs have also been shown to control synaptic potentiation associated with neurological and psychiatric disorders, which have opened unimaginable scenarios a few years ago.

The aim of this Research Topic is to describe and discuss research on known and already tested compounds (until the toxicology analysis/Phase I stage at least) and their potential new uses, including new versions, new indications, and other novel applications. The collection aims to provide an in-depth analysis of old drugs and their role in the development of new drugs that are effective in treating different types of diseases. Overall, the main goal of this collection is to showcase how the study of old drugs can contribute to the creation of better, more effective and personalized-adjusted drugs through the discovery of new indications, improvement of efficacy, creation of new formulations or products, leading to better patient outcomes.

The Research Topic is focused on an overview of old drugs and their alternative modes of action, potential use in other indications, and future drug discovery strategies. The collection welcomes in-depth reviews, mini-reviews, original research, perspectives, and case studies which will delve into the molecular and cellular pathways of these drugs and how they present unique opportunities for the discovery of new drug targets. Manuscripts should contain meaningful research on the following topics, but are not limited to:

• the presentation of a new mechanism of action for old drugs that may become valuable in the treatment of certain diseases such as cancer, autoimmune, neurodegenerative disorders, psychiatric conditions, anesthetics and monogenic diseases.
• presentation of a new mechanism of action for existing drugs, which may become a target for other substances;
• presentation of new applications for already existing and used drugs;
• presentation of drugs that, subjected to minor modifications, such as the use of an isomer and not a racemate, the use of a metabolite, use in the form of an ester and not a salt, gives it different properties and therapeutic possibilities;
• presentation of drugs in which the mechanisms of action that cause side effects have been converted into beneficial effects, e.g. anticancer use.