Control of the activity of therapeutic compounds by means of light can be achieved with photolabile compounds. Caged drugs are inactive compounds that become active when they are irradiated locally in a tissue or specific area of the body with light with a specific wavelength to control the dose and site of action of the drug. Different receptors and enzymes are being currently studied in the group.
As an example, the compound JF-NP-26, a coumarin-caged derivative of raseglurant, a mGlu5 receptor negative allosteric modulator that allows a photoregulation of drug activity. Illumination of JF-NP-26 induces a photochemical reaction releasing the active drug, which effectively controls mGlu5 receptor activity both in ectopic expressing systems and in striatal primary neurons.
After systemic administration of JF-NP-26 in mice, local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induces light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models.
This is the first example of photocontrol of analgesia in vivo using a caged mGlu5 receptor negative allosteric modulator. This technology can have application in the treatment of chronic diseases that require precise control of the activity of the drug.