The action and adsorption of local anesthetic enantiomers on erythrocyte and synaptosome membranes

Abstract 1. 1. Two local anesthetics which were enantiomers of one another (spirosuccinimides RAC 109 I and II) protected human erythrocytes from hypotonic hemolysis at concentrations known to cause local anesthesia (0.35–1.6 mM). Both enantiomers produced 40 % anti hemolysis at 1.6 mM. The threshold concentration for anti-hemolysis with RAC 109 I extrapolated back to 1.15·10 −4 M, while that with RAC 109 II extrapolated to 1.92·10 −4 M. 2. 2. The adsorptions of RAC 109 I and RAC 109 II to erythrocyte membranes were identical. The adsorptions of the two optical isomers to isolated synaptosomes (guinea pig brain) were also identical. All these adsorption isotherms were unaffected by the addition of 1 mM Ca 2+ . 3. 3. The membrane/buffer partition coefficients of the anesthetics on synaptosome membranes were identical to those on erythrocyte membranes. 4. 4. The membrane/buffer partition coefficients were not constant, but varied inversely with the free concentration of the local anesthetic. Increasing the ionic strength also reduced the membrane/buffer partition coefficients, regardless of the free concentration. 5. 5. At the exitability-blocking concentration of 2.5 mM, the concentration of local anesthetic in the membrane phase was about 0.02 mole drug per kg of dry membrane.