ISAXONINE BASE IS A STRONG PERTURBER OF PHOSPHOLIPID-BILAYER ORDER AND FLUIDITY A DIFFERENTIAL SCANNING CALORIMETRY AND SPIN LABELING STUDY

The effects of the neurotropic drug isaxonine on fully hydrated dipalmitoyl-phosphatidylcholine (DPPC) bilayers was studied in the temperature range 0.degree.-60.degree. C, using differential scanning calorimetry and ESR spectroscopy, with 2 stearic acid spin labels. At low concentration (1% mol/mol), isaxonine is trapped in the polar interface and enhances the phospholipid multibilayers organization in the gel state. At high concentration (30% mol/mol), the drug disorganizes the phospolipidic structures and may induce domain formation by phase separation. The strong interactions of isaxonine at the lipid-water interface change the ionization state of the stearic acid spin labels which become totally ionized. Then isaxonine acts as a modifier of the surface pH of the bilayer. The strong membrane effects of isaxonine may explain in part its pharmacological properties in vivo.