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.

Divergent interaction profiles of gabapentin and levetiracetam with dipalmitoylphosphatidylcholine lipids

“…By following the previous reports 18,20 DPPC MLVs in the absence and presence of GBP and LEV (1-5-10-20 mol%) were prepared. Briefly, 5 mg DPPC lipids were dissolved in chloroform and evaporated under nitrogen flow and desiccated under vacuum overnight to remove solvent.…”

“…Relatively, with aiming to provide a general perspective about how GBP and LEV incorporate into membrane lipids their interactions with dipalmitoylphosphatidylcholine (DPPC) multilamellar vesicles (MLVs) were comparatively investigated in the present study; as earlier works performed for different kinds of molecules. [18][19][20] DPPC phospholipid bilayers used in the current work are considered suitable model systems to mimic cell membranes, and thus to study membrane structure and properties since phosphatidylcholines (PCs) are major lipid components of eukaryotic cell membrane. Additionally, their structural and thermodynamic properties are well-defined, which may be needed for the research of drug-lipid interactions.…”

“…Additionally, their structural and thermodynamic properties are well-defined, which may be needed for the research of drug-lipid interactions. 18,20 Thus, the interactions of GBP and LEV with DPPC MLVs in terms of lipid phase behavior, order and dynamics and hydration state of the polar part of DPPC MLVs were examined using differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy, which have not been previously reported to the best of our knowledge.…”

Potent antidiuretic agonists, deamino‐vasopressin and desmopressin, and their inverso analogs: NMR structure and interactions with micellar and liposomic models of cell membrane

“…There is a lot of lipids used as models of the cell membrane; some of them in aqueous environment undergo self‐organization into liposomes and others into micelles . Zwitterionic phosphatidylcholine lipids have been considered to provide convenient models of eukaryotic cell membrane, especially with addition of small amounts of anionic phosphoglycerol lipids, which mimic a slight prevalence of a negative charge on the plasma membrane surface . However, in water the lipids undergo self‐organization into liposomes, which makes them unsuitable for solution NMR spectroscopy.…”

The chain order of binary unsaturated lipid bilayers modulated by aromatic-residue-containing peptides: an ATR-FTIR spectroscopy study

“…It provides valuable information about biomembranes: the phase transition and order-disorder state of lipid membranes, 23 the asymmetry and assemblies of bilayers,…”