Concentration effects of sumatriptan on the properties of model membranes by molecular dynamics simulations.

In this work, we report a molecular dynamics simulations study of protonated sumatriptan (pSMT) in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline at the fluid lamellar phase. The simulations were carried out at three different drug/lipid stoichiometries, 1:75, 1:10 and 1:3, under NPT conditions. Our results show partition of pSMT between the lipid head-water interphase and water phase. The main interactions that stabilized the systems were hydrogen bonds, salt bridges and cation-π. Besides, pSMT molecules have no access to the hydrophobic region of the bilayer at the studied concentrations. From an atomistic point of view, this work could contribute to the discussion of drug-membrane interactions regarding the limitation of sumatriptan to cross the blood-brain barrier.