Biphasic effect of local anesthetic carbisocaine on fluidity of phosphatidylcholine bilayer.

The local anesthetic carbisocaine (1), the monohydrochloride of [2-(heptyloxy)phenyl]-2-(diethylamino)-1-methylethyl ester of carbamic acid, exerts a biphasic effect on the fluidity of egg yolk phosphatidylcholine model membranes as detected by the stearic acid spin probes with the paramagnetic doxyl group bound to C-5 or C-16. The fluidity initially increases with an increase in the concentration of 1, but at concentrations above 25 mmol/l a decrease of fluidity has been observed. 31P NMR spectroscopy indicates changes in the phosphocholine head-group conformation in the presence of 1. The decrease of fluidity is caused by the increased packing density in the bilayer hydrophobic region at high concentrations of 1, probably due to interdigitation of hydrocarbon chains from apposing monolayers in the hydrophobic center of the bilayer.