Triptan partition in model membranes

I. WOOD; M. PICKHOLZ

Sierra de la ventana

Conferencia; XLIII Reunión Anual Sociedad Argentina de Biofisica; 2014

Sociedad Argentina de Biofisica

Triptan partition in model membranes Wood, I1,2*; Pickholz, M1,2 1Inst. NANOBIOTEC (CONICET?UBA), Junín 956, 6° Piso, CABA; 2CONICET *irewood@gmail.com Triptans are drugs based on the serotonin (5-HT) structure used for the migraine treatment, since their action as receptor 5-HT1B/1D/1F selective agonists [1]. In the present work we have conducted molecular dynamics simulations of protonated triptans, sumatriptan and naratriptan, in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC). We have carried out simulations of two concentrations for each drug. Our results show partition between the lipid head-water interphase and water phase for both triptans, with increasing access to the water phase with increasing concentrations. The triptans were stabilized at the interphase through different specific interactions with the POPC bilayer such as hydrogen bonds, salt bridges, and cation-π. Besides, sumatriptan and naratriptan protonated molecules have no access to the hydrophobic region of the bilayer at the studied conditions. Similar results were found for both drugs, however protonated naratriptan shows slightly higher affinity for the water phase. This behavior was attributed to the bulky lateral amino group in its structure under the studied conditions (drugs originally placed at the water phase). This work represents a first insight to the comprehensive understanding and comparison of triptan partition in model membranes. (Subir en formato Word al sitio https://easychair.org/conferences/?conf=sab2014) Acknowledgements: ANPCyT, UBA, CONICET References 1- Humphrey PPA. Ann NY Acad Sci. 1990. 587