Abstract
Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson’s disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine. Furthermore, DHA displays properties that may lead to its use as a neuroprotective agent. In the present study, we constructed a novel bivalent ligand covalently linking caffeine and DHA and assessed its pharmacological activity and safety profile in a simple cellular model. Interestingly, the new bivalent ligand presented higher potency as an A2AR inverse agonist than caffeine alone. We also determined the range of concentrations inducing toxicity both in a heterologous system and in primary striatal cultures. The novel strategy presented here of attaching DHA to caffeine may enable increased effects of the drug at desired sites, which could be of interest for the treatment of PD.
Highlights
Caffeine, the most consumed psychoactive substance worldwide, is generally used because it enhances physical and cognitive functions, improving alertness, physical performance and concentration, while decreasing fatigue [1,2]
We recently reported that caffeine may act as an inverse agonist for adenosine A2A receptors (A2A R)
We have synthesized a novel drug by combining caffeine and Docosahexaenoic acid (DHA) using a simple and efficient synthetic procedure
Summary
The most consumed psychoactive substance worldwide, is generally used because it enhances physical and cognitive functions, improving alertness, physical performance and concentration, while decreasing fatigue [1,2]. Caffeine is used as an adjuvant drug in pain relief [3]. Several epidemiological studies have revealed an inverse relationship between caffeine consumption and the risk of developing. PD [5,6,7], suggesting that caffeine can act as a neuroprotective agent [8,9]. The mechanism of action of caffeine, at non-toxic concentrations, involves interacting with and blocking adenosine receptors [10]. We recently reported that caffeine may act as an inverse agonist for adenosine A2A receptors (A2A R)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
