Scientists at the Institute of Neurosciences of the University of Barcelona helped develop the first light-activated drug, called JP-NP-26, for the treatment of pain. This novel strategy may revolutionize how we treat pain disorders such as fibromyalgia.

The study, “Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator,” was published in the journal eLife.

The development of drugs according to existing pharmacology is often impaired by constrains such as the difficulty in following the drug in time once delivered, the time required to assess the correct dosages, and cases where the drug is slow or affects multiple tissues.

A new field in pharmacology called optopharmacology was developed to overcome some of these constrains. This new discipline uses light to control drug activity. This means that if a drug is developed to be light-sensitive, then scientists can actually control the drug’s activity in a spatial and temporal manner.

The study reports the development of a “photo-drug” – called JF-NP-26 – that demonstrated a potent therapeutic value for treating pain.

“In the clinical field, there is not any precedent of the uses of optopharmacology to improve pain treatment or any disease associated with the nervous system. This is the first light-activated drug designed for the treatment of pain in vivo with animal models,” Prof. Francisco Ciruela at the University of Barcelona and the study’s co-lead author, said in a press release.

In this new optopharmacology approach, scientists can use an analgesic for which the mechanism of action is known, and turn it into a photosensitive and inactive drug. Using light with a certain wavelength, the drug can be activated in a targeted and precise region, such as the brain or skin.

JF-NP-26 is also called photocaged, since it only exerts its activity when activated by light. Without light, it remains inactive.

In fact, when compared to other photosensitive compounds, JF-NP-26 shows no effect inside an animal until a specific beam of light (in this case, 405 nm wave length) hits the target tissue. Of note, JF-NP-26 showed no toxic or unwanted effects even in high dosages.

The strategy is based on the release of the active molecule called raseglurant when the drug receives light. This molecule is then free to block the metabotropic glutamate type 5 (mGlu5) receptor, responsible for propagating neuronal pain.

“The molecule created by the action of the light, the raseglurant, does not belong to any group of drugs from the classic anti-pain list of drugs: non-steroidal anti-inflammatory drugs or NSAID (paracetamol, ibuprofen, etc.) and opioids (morphine, phentanyl),” Ciruela said. “Consequently, this study describes an analgesic mechanism which has not been explored enough so far.”

“Actually, the raseglurant was examined in clinical trials as an analgesic to treat migraine but it was ruled out due its hepatoxicity,” he added. “This new optopharmacology of the raseglurant can stop adverse effects in the liver and opens a new path to start using it as an analgesic.”

Optopharmacology may represent a potential new strategy for redefining the way we treat pain in fibromyalgia and other diseases. It may also help reduce the unwanted effects of several of the current drugs, such as morphine, and its high risk of addiction.

“If we compare natural biological molecules that act in living beings with drugs, we can see that the former can work with great precision, acting in centralized areas and with regulated doses, with defined lengths,” said second co-lead author Amadeu Llebaria, from the Medicinal Chemistry & Synthesis group of the Institute of Advanced Chemistry of Catalonia.

“However, the drugs we have act in all areas and without a strict control. The use of light-controlled molecules tries to complete these spaces to get more precise drugs that can act like biological molecules,” LLebaria said.