Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions with light. We have obtained a series of phenylazopyridines with light dependent activity as negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu₅). Here we describe the factors needed to achieve an operational molecular photoisomerization and its effective translation into in vitro and in vivo receptor photoswitching, which includes zebrafish larva motility and the regulation of the antinociceptive effects in mice. The combination of light and some specific phenylazopyridine ligands displays atypical pharmacological profiles, including light-dependent receptor overactivation, which can be observed both in vitro and in vivo. Remarkably, the localized administration of light and a photoswitchable compound in the peripheral tissues of rodents or in the brain amygdalae results in an illumination-dependent analgesic effect. The results reveal a robust translation of the phenylazopyridine photoisomerization to a precise photoregulation of biological activity.

A gas chromatography-mass spectrometry (GC-MS) method was used for the simultaneous quantitation of 3,4-methylenedioxymethamphetamine (MDMA) and the 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-methoxyamphetamine (HMA) metabolites in plasma and urine samples after the administration of 100 mg MDMA to healthy volunteers. Samples were hydrolyzed prior to a solid-phase extraction with Bond Elut Certify^® columns. Analytes were eluted with ethyl acetate (2% ammonium hydroxide) and analyzed as their trifluoroacyl derivatives. Linear calibration curves were obtained at plasma and urine concentration ranges of 25–400 ng/mL and 250–2000 ng/mL for MDMA and HMMA, and of 2.5–40 ng/mL and 100–1000 ng/mL for MDA and HMA. Following the same urine preparation procedure but without the derivatization step, a capillary electrophoresis (CE) method for enantiomerical resolution of compounds was developed using (2-hydroxy)propyl-β-cyclodextrin at two different concentrations (10 and 50mM in 50mM H₃PO₄, pH 2.5) as chiral selector. Calibration curves for the CE method were prepared with the corresponding racemic mixture and were linear between 125 and 2000 ng/mL, 50 and 1000 ng/mL, and 125 and 1500 ng/mL for each enantiomer of MDMA, MDA, and HMMA, respectively. Stereoselective disposition of MDMA and MDA was confirmed. HMMA disposition seems to be in apparent contradiction with MDMA findings as the enantiomer ratio is close to 1 and constant over the time.