Аннотация:We have studied the influence of local anesthetics on the permeability of phospholipid liposomes of various compositions to calcein. We have tested amide (lidocaine, prilocaine, mepivacaine and bupivacaine) and ester anesthetics (benzocaine, procaine and tetracaine). The permeability of large unilamellar liposomes to calcein was determined by measuring the relative intensity of fluorescence of calcein released from vesicles. It has been showed that all tested amide anesthetics slightly affect the leakage of calcein from dioleoylphosphocholine (DOPC) liposomes. The most effective amide has been bupivacaine. Substitution in the membranes of 20 mol % DOPC on tetraoleoylcardiolipin (TOCL) has been accompanied by increased activity of amides. Benzocaine and procaine at concentration up to 100 mM practically have not changed DOPC liposome permeability. Addition of tetracaine up to concentration of 2 mM has not affected the permeability of vesicles, further increasing in the concentration up to 50 mM has led to increase in the intensity of calcein fluorescence and at a concentration of 100 mM a complete engagement of fluorescent marker has been observed. In the case of vesicles, including 20 mol % TOCL, the threshold concentration of tetracaine and the concentration caused 100%-leakage have been 7 and 20 mM, respectively. Using the confocal fluorescence microscopy of giant unilamellar vesicles made from equimolar mixture of DOPC and tetramyristoylcardiolipin (TMCL) we have shown that anesthetics destroy solid ordered domains, and this ability has increased in the row of procaine ≈ mepivacaine < bupivacaine << tetracaine. The revealed difference in the influence of local anesthetics can be caused by different depth of immersion of anesthetics into membrane.