CALORIMETRIC STUDY OF THE INTERACTION OF LOCAL-ANESTHETICS [2-(ALKYLOXY)PHENYL]-2-(1-PIPERIDINYL)ETHYL CARBAMATES WITH MODEL DIPALMITOYLPHOSPHATIDYLCHOLINE MEMBRANES

Local anesthetics of the homologous series of monohydrochlorides of [2 -(alkoxy)phenyl]-2-(1-piperidinyl)ethyl esters of carbamic acid decrea se the temperature of phase transitions L(beta') --> P-beta (pretransi tion) and P-beta --> L(alpha) (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. F or n > 6 no pretransition could be detected. The efficiency in decreas ing the temperature of the main transition increases up to n = 8 - 9 w hile it starts decreasing at n = 10. Computer simulation of the thermo grams has shown that the decrease of efficiency at n = 10 is caused by the dependence of the partition coefficients of the anesthetics K-P,K -G and K-P,K-LC between the aqueous phase and the P-beta and L(alpha) phases, respectively, on the length of the alkoxy substituent, thus: l og K-P,K-LC = A(LC) + B-LC n and log K-P,K-G = A(G) + B-G n, where B-L C < B-G.