FACTORS INFLUENCING LOCAL ANESTHETIC BLOCKADE

It is generally considered that local anesthetics act directly at the level of the plasma membrane (10, 23, 45). In addition to their anesthetic effects on excitable membranes (4, 45, 50), local anesthetics produce a variety of effects on membranes, including expansion (47), altered osmotic fragility (46), and inhibition of cell spreading (43), movement (13, 40), adhesion (31, 42), and fusion (36). Several studies have shown that local anesthetics interact with membrane lipids (4, 7, 11, 14, 18, 33, 35, 45), particularly acidic phospholipids (14, 33, 35, 45), and are also able to displace Ca 2+ from membranes (7, 33, 34, 48). Local anesthetics are considered to interact with membranes by both hydrophobic and electrostatic interactions in close proximity with the anionic groups of acidic phos. pholipids (7, 14, 35). Local anesthetics are known to produce molecular disordering in lipid bilayers and to enhance the fluidity of phospholipids in membranes (20, 35). These effects occur only at very high anesthetic concentrations and are probably not related to anesthesia. At much lower concentrations, tertiary amine local anesthetics cause modifications in cell agglutinability (37 39) and mobilities of certain surface receptors (37-39, 47). Specifically, these receptors appear to be "uncoupled" from cytoplasmic controls (37-39), which appear to correspond to cytoskeletal elements associated with the plasma membrane (38, 39, 43, 47). We have