Photopharmacology is a way to activate drugs in specific areas of the body using light. This innovative approach involves altering the chemical structure of a drug by adding a light-activated molecular switch, such as azobenzene. This allows the drug to be activated only when exposed to a specific color of light, rather than in the dark.
Based on these principles, a team of researchers led by the Institute of Bioengineering of Catalonia (IBEC) has developed photosensitive derivatives of carbamazepine, an antiepileptic drug widely used in medicine to combat certain types of neuropathic pain, such as trigeminal neuralgia. These compounds, which have an analgesic effect when activated by light, are able to inhibit nerve signals locally and on demand. The derivatives synthesized by the researchers are activated at wavelengths corresponding to the amber color, which allows them to pass through tissues and bones using conventional halogen lamps.
The two compounds synthesized, carbazopine-1 and carbadiazocine, exhibit photopharmacological activity, allowing the activity of hippocampal neurons and the locomotion of zebrafish larvae to be reversibly controlled by light. These in vivo experiments allow the observation of anxiety-related behaviors that result in abrupt swimming movements. Luisa Camerin, a researcher at IBEC and first author of the study, explains: “When we illuminate the larvae that have absorbed these compounds with a certain wavelength, the drug is activated and the larvae move faster. If we change the wavelength, their movement slows down again, demonstrating the reversible effect of the compound on the nervous system.
Carbadiazocine has also demonstrated analgesic properties: “In rat models developed in Esther Berrocoso’s laboratory at the University of Cadiz, we observed that carbadiazocine had an analgesic effect on neuropathic pain without any signs of anesthesia, sedation or toxicity. These results demonstrate a simple and convincing treatment with non-invasive illumination,” explains Pau Gorostiza, ICREA research professor, principal investigator at IBEC and member of CIBER-BBN.
Neuropathic pain is caused by injuries or diseases of the somatosensory system, such as lumbar radiculopathy (“sciatica”), diabetic neuropathy, and chronic postoperative pain. Treatment of this type of pain often requires opioids, which are more potent analgesics than the usual NSAIDs, such as paracetamol and ibuprofen. However, their use is controversial because of their variable effectiveness, the need for high doses that can lead to tolerance and dependence, and systemic side effects such as constipation, nausea, dizziness, and drowsiness.
In this context, light-based therapies are becoming increasingly important in medicine due to their ability to target specific regions of the body, thereby increasing treatment efficacy and reducing side effects of systemic drugs.
The team is already working on the next stage of this project, which will involve activating the drugs using infrared light, which penetrates deeper into tissues, and using portable light sources such as lasers or light-emitting diodes (LEDs).
This study is part of the PHOTOTHERAPORT project, coordinated by the Institute of Bioengineering of Catalonia (IBEC). The project is funded by the prestigious Pathfinder Open program of the European Innovation Council (EIC) and focuses on the development of luminescent implants and light-activated drugs for innovative neuromodulation therapies (HORIZON-EIC-2023 PATHFINDEROPEN-01 program, n° 101130883). PHOTOTHERAPORT is a consortium of 8 institutions from 4 countries with a budget of 3 million euros over 3 years to carry out the project.
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