Flunitrazepam overcompensates the effects of lidocaine on thermotropic equilibrium of dipalmitoyl phosphatidyl-choline

SANCHEZ, JM;; BIANCONI, L; GARCIA, DA; DE PAULA, E; MA PERILLO

Bariloche Rio Negro. Argentina

Otro; XXXII Reunion Anual de SAB; 2003

Sociedad argentina de Biofísica

Previously, by analysing erutrocyte mophology, we demosntrated that in the presence of either flunitrazepam (FNT) or lidocaine (LC) the plasma membrane curvature changed but in opposite directions. Moreover, each drug could compensate the effect of the other one in a dose dependent manner (Chem. Biol.Int. 129 (2000) 263). In order to get deeply in the molecular mechanismof these phenomena, in the present work we investigated by HDSC the effect of FNT, LC and FNT+LC on the stability of MLVS of dpPC. Only in samples submitted to a second temperature scanning, LC decreased both the enthalphy (DHp) as well as the temperature (TMP) of the pretransition (Lb----Pb) and increased the width of the heat absortion peak, reflecting a decrement in the cooperative of the phase transition. The presence of 59 mM FNT, reverted the effect of  LC on TMp and tended to increase DHp above the values obtainde with the control (dpPC without any drug). FNT alone increased the DH of both pre and main transition. The former was reverted by LC. The effects of LC on decreasing TMP and TMC were also observed in the oresence of FNT. The relative concentration of each drug in the bilayer, their eeffects on hydrogen bonds network and water structure at the lipid water interface.