Collect. Czech. Chem. Commun. 1995, 60, 763-780

Calorimetric Study of the Interaction of Local Anesthetics [2-(Alkyloxy)phenyl]-2-(1-piperidinyl)ethyl Carbamates with Model Dipalmitoylphosphatidylcholine Membranes

Jana Gallováa, Jaroslava Bágeľováb, Jozef Čižmárikc and Pavol Balgavýa

a Department of Physical Chemistry, Comenius University, 832 32 Bratislava, Slovak Republic
b Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, 043 53 Košice, Slovak Republic
c Department of Pharmaceutical Chemistry, Comenius University, 832 32 Bratislava, Slovak Republic


Local anesthetics of the homologous series of monohydrochlorides of [2-(alkoxy)phenyl]-2-(1-piperidinyl)ethyl esters of carbamic acid decrease the temperature of phase transitions Lβ' → Pβ (pretransition) and Pβ → Lα (main transition) of 1,2-dipalmitoyl-sn-phosphatidylcholine in aqueous phase at pH 6.2. The efficiency of the anesthetics in decreasing the pretransition temperature increases with the number of carbon atoms n of the alkoxy substituent up to n = 6. For n > 6 no pretransition could be detected. The efficiency in decreasing the temperature of the main transition increases up to n = 8 - 9 while it starts decreasing at n = 10. Computer simulation of the thermograms has shown that the decrease of efficiency at n = 10 is caused by the dependence of the partition coefficients of the anesthetics KP,G and KP,LC between the aqueous phase and the Pβ and Lα phases, respectively, on the length of the alkoxy substituent, thus: log KP,LC = ALC + BLC n and log KP,G = AG + BG n, where BLC < BG.