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-phosphatidyl-choline (DPPC) bilayers has been studied in the temperature range 0 degree-60 degrees, using differential scanning calorimetry and electron spin resonance spectroscopy, with two 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. In contrast, at high concentration (30% mol/mol), the drug disorganizes the phospholipidic 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.
D002152:Calorimetry, Differential Scanning; D004578:Electron Spin Resonance Spectroscopy; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects*; D009994:Osmolar Concentration; D010743:Phospholipids / Q000378:metabolism*; D011663:Pulmonary Surfactants; D011743:Pyrimidines / Q000494:pharmacology*; D013113:Spin Labels; D013696:Temperature
D008051:Lipid Bilayers; D010743:Phospholipids; D011663:Pulmonary Surfactants; D011743:Pyrimidines; D013113:Spin Labels; C020375:isaxonine