Binding Ability of Lacosamide to Phosphatidylcholine Lipids and Cholesterol Effects

Abstract

Aim: In the present study, in order to obtain information about binding profile of lacosamide (LCM) with membrane lipids, which is the most important parametre that determines its availability in the central nervous system, we aimed to analyze molecular interaction of LCM with model membranes formed by well-known representative lipids of biological membranes. Methods: The effects of varied concentrations (1-10-20 mol %) of LCM on biophysical parameters of dipalmitoylphosphatidylcholine multilammelar vesicles in the absence and presence of cholesterol (10 mol %) were studied by differential scanning calorimetry and fourier transform infrared spectroscopy. Results: According to the data obtained in all concentrations LCM decreased main transition temperature and enthalpy with broaden transition curve. However, LCM at 1 mole % affected such values mostly in comparison with 10-20 mol% concentrations. With the addition of CHO to 20 mol % of LCM sample, these parameters were significantly lowered. Moreover, LCM at high concentrations prominently increased both order of lipid phases, and hydrogen binding capacity of glycerol and phosphate groups of lipids but reduced fluidity. Also, CHO was found to tend to reverse these effects of LCM except for order and fluidity parameters. Conclusion: According to the findings obtained, in accordance with its chemical structure, LCM leads to alteration of thermotrophic parameters, structures and functions of phosphatidylcholine lipids abundant in brain cell membrane, which also show the penetration ability of LCM into biological membranes. But, the degree of such behavior can be dependent on applied concentration of LCM and presence of CHO. In summary, all data may provide information for its use in therapeutic strategies of epilepsy and development of new antiepileptics.