Ionization and adsorption of a series of local anesthetics in detergent micelles: studies of drug fluorescence.
The goal of this study was to compare the behavior of structurally homologous local anesthetics (LAs) adsorbed to a simplified membrane model. Interactions of LAs with micelles made from negative and neutral detergents were assayed by drug fluorescence. Micellar:drug affinity, equivalent dielectric constant and pKa of bound LAs were assessed for procaine, tetracaine, procainamide, benzocaine and aminoparabenzyldiethylamine, a procaine homologue containing an alkyl chain instead of an ester bond. Shifts in maximum emission wavelength and changes in fluorescence intensity showed that 1) increased LA hydrophobicity (expressed as octanol:buffer partition coefficient) corresponded to increased affinity for all micelles; 2) protonated species of LA were bound more tightly than neutral species to negative micelles, but less tightly to unchanged micelles; 3) drugs with larger dipole moments (amide < ester < alkyl) bind less tightly to micelles than those with smaller dipoles; 4) Larger dipole moments of LAs also result in a larger equivalent dielectric constant around the micellar-bound LAs, meaning that the LA binds at a shallower depth from the micelle surface; and 5) binding the neutral micelles lowers the pKa but binding to negatively charged micelles raises the pKa (due to the concentrating effects of surface charge on H+). The results provide a picture of interfacial adsorption of LAs in a relatively simple system that should allow interrelation of the dipole field contributions to LA behavior in phospholipid bilayers.
Desai
S
S
Anesthesia Research Laboratories, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
Hadlock
T
T
Messam
C
C
Chafetz
R
R
Strichartz
G
G
D000327:Adsorption; D000779:Anesthetics, Local / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D003902:Detergents / Q000494:pharmacology*; D005453:Fluorescence; D008823:Micelles
D000779:Anesthetics, Local; D003902:Detergents; D008823:Micelles