The local anesthetic tetracaine destabilizes membrane structure by interaction with polar headgroups of phospholipids.

The effect of the local anesthetic tetracaine at less than 10 mM on the water permeability of the phospholipid membrane was examined using liposomes composed of various molar ratios of negatively charged cardiolipin to electrically neutral phosphatidylcholine by monitoring their osmotic shrinkage in hypertonic glucose solution at 30 degrees C. The concentration of tetracaine causing the maximum velocity of shrinkage of liposomes increased with increase in the molar ratio of cardiolipin. Tetracaine increased the zeta-potential of the negatively charged liposomal membrane toward the positive side due to the binding of its cationic form to the negatively charged polar headgroups in the membrane. The maximum velocity of water permeation induced by osmotic shock was observed at essentially the same tetracaine concentration giving a zeta-potential of the liposomal membrane of 0 mV. These concentrations were not affected by change in the sort of acyl-chain of phospholipids in the liposomes when their negative charges were the same. These results suggests that the membrane integrity is governed mainly by the electrical charge of phospholipid polar headgroups when phospholipid bilayers are in the highly fluid state, and that positively charged tetracaine molecules neutralize the negative surface charge, lowering the barrier for water permeation through phospholipid bilayers.