title: Agomelatine strongly interacts with zwitterionic DPPC and charged DPPG membranes.
abstract: Depression is one of the most common psychiatric diseases in the population. Agomelatine is a novel antidepressant drug with melatonin receptor agonistic and serotonin 5-HT2C antagonistic properties. Furthermore, being a melatonergic drug, agomelatine has the potential of being used in therapeutic applications like melatonin as an antioxidant, anti-inflammatory and antiapoptotic drug. The action mechanism of agomelatine on the membrane structure has not been clarified yet. In the present study, we aimed to investigate the interaction of agomelatine with model membranes of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylgylcerol (DPPG) by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). We found that agomelatine interacts with the head group in such a manner that it destabilizes the membrane architecture to a large extent. Thus, agomelatine causes alterations in the order, packing and dynamics of the DPPC and DPPG model membranes. Our results suggest that agomelatine strongly interacts with zwitterionic and charged membrane phospholipids. Because lipid structure and dynamics may have influence on the structure of membrane bound proteins and affect the signal transduction systems of membranes, these effects of agomelatine may be important in its action mechanism.
authors.affiliation: Middle East Technical University, Department of Biological Sciences, 06800 Ankara, Turkey.
authors.forename: Seza
authors.initials: S
authors.lastname: Ergun
authors.affiliation: Middle East Technical University, Department of Biological Sciences, 06800 Ankara, Turkey.
authors.forename: Pinar
authors.initials: P
authors.lastname: Demir
authors.affiliation: Uskudar University, Neuropsychopharmacology Application and Research Center, 34662 Istanbul, Turkey.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Uzbay
authors.affiliation: Middle East Technical University, Department of Biological Sciences, 06800 Ankara, Turkey. Electronic address: feride@metu.edu.tr.
authors.forename: Feride
authors.initials: F
authors.lastname: Severcan
keywords: Agomelatine; DSC; FTIR spectroscopy; Lipid structure; Membrane lipid