A team of the Institute of Neurosciences of the University of Barcelona has participated in the design of the first light-activated drug, the JF-NP-26, for the treatment of pain, according to a research with animal models published in the journal, eLife.

The new study is conducted by the teams led by Professor Francisco Ciruela, from the Faculty of Medicine and Health Sciences of the University of Barcelona, the Institute of Neurosciences of the UB and the Bellvitge Biomedical Research Institute (IDIBELL), and Amadeu Llebaria, from the MCS group of the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC).

In general, common pharmacology has important limitations -slow and inexact distribution of the drug, lack of spatiotemporal traits in the organism, difficulties in the dose adjustments, etc.- which can limit the therapeutic action of any drug. In this context, optopharmacology is an emerging discipline in pharmacology, based on the use of light to control drug activity. Therefore, using light on a photosensitive drug, the pharmacological process can be controlled with spatial and temporal precision.

The new study has come up with the design of a ‘photo-drug’ (JF-NP-26) with powerful therapeutic applications to treat pain, a molecule that can be specifically activated at any wished moment (that is, with a high spatiotemporal resolution) with light.

‘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,’ said Professor Francisco Ciruela.

In this new optopharmacology proposal, a drug with a known action mechanism (for example an analgesic) is chemically modified to make it photosensitive and inactive. This drug is activated when receiving light -using an optical fiber- of a suitable wave length and with an exact precision on the target tissue (brain, skin, articulations, etc.).

The drug JF-NP-26 is also called photocaged, a chemically and inactive covered molecule which is activated with light. Compared to other photosensitive compounds, JF-NP-26 is a molecule that has no pharmacological effect on an animal until the target tissue received light from a visible spectrum (405 nm wave length). Moreover, JF-NP-26 does not show toxic or unwanted effects even if the dose is high -in short-length studies on animals.

The drug’s lightening includes a treatment on the molecule that releases the active molecule (raseglurant) that blocks the metabotropic glutamate type 5 (mGlu5) receptor, found in lots of neuronal functions such as the spread of neuronal pain. Blocking this receptor allows preventing the pain from spreading into the brain. This can be produced both due the outlying neurons and the central nervous system (brain) and create, in both cases, an analgesic effect as a result.

‘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).

‘Consequently, this study describes an analgesic mechanism which has not been explored enough so far,’ said Ciruela.

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