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

I. WOOD; M. PICKHOLZ

Villa Carlos Paz, Córdoba

Congreso; Reunión anual de la sociedad de Biofísica Argentina; 2013

SAB

Concentration Effects of Sumatriptan on the Properties of Model Membranes Wood, I. 1* and Pickholz, M. 1,2 1Departamento de Tecnología Farmacéutica, FFyB, UBA; 2CONICET *irewood@gmail.com Triptans are drugs rationally designed based on the neurotransmitter serotonin (5-HT) and used for the treatment of migraine [1], acting as receptor selective agonists 5-HT1B/1D/1F [2]. In this work, we report a Molecular Dynamics (MD) simulations study of the first designed triptan, Sumatriptan, at protonated state (pSMT), in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC). The simulations were carried out at three different drug/lipid stoichiometries: 1:75, 1:10 and 1:3, under NPT conditions. The goal of this study is to evaluate the effects of different concentrations pSMT on the lipid bilayer properties. Our results show partition of pSMT between the lipid head-water interphase and water phase. The orientation of PN vector was altered by the presence of pSMT at lipid-water interphase, showing concentration dependence. 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 the drug-membranes interactions regarding the limitation of Sumatriptan to cross the blood-brain barrier, that could be associated with both the efficacy and adverse effects. References 1- Humphrey PPA. Ann NY Acad Sci. 1990. 587 2- Rapoport AL. J Headache Pain. 2001. S87