Cell membrane fusion by chloroprocaine

Abstract

The cytotoxicity of the local anesthetics chloroprocaine, procaine, and lidocaine was studied in murine and human cells. Murine glial and hepatic cells, and human fibroblasts were individually exposed to chloroprocaine, procaine, and lidocaine in concentrations ranging from 1.6 X 10(-3) M to 0.2 X 10(-3) M. The cells of all three cell lines underwent membrane fusion after exposure to chloroprocaine as indicated by the presence of the high number of multinucleated cells in the cultures. The 0.8 X 10(-3) M concentration was the most fusogenic, and caused multinucleation in 30% of glial and hepatic cells, and in 23% of fibroblasts. Membrane fusion and multinucleation also occurred in mixed human and murine cell cultures that were exposed to 0.8 X 10(-3) M concentration of both commercial and crystalline solutions of chloroprocaine, with a portion of multinucleated cells that was 27 and 17%, respectively. Cell membrane fusion was not caused by procaine, lidocaine, sodium bisulfite (the antioxidant present in the commercial solutions of chloroprocaine), or chloro-aminobenzoic acid and diethylamino-ethanol (the two chloroprocaine metabolites). The fusogenic effect of chloroprocaine on cell membrane has not been previously described for any local anesthetic.