Ionization and adsorption of a series of local anesthetics in detergent micelles: studies of drug fluorescence. 1994

S Desai, and T Hadlock, and C Messam, and R Chafetz, and G Strichartz
Anesthesia Research Laboratories, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.

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.

UI MeSH Term Description Entries
D008823 Micelles Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as EMULSIONS. Micelle
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D003902 Detergents Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. Cleansing Agents,Detergent Pods,Laundry Detergent Pods,Laundry Pods,Syndet,Synthetic Detergent,Agent, Cleansing,Agents, Cleansing,Cleansing Agent,Detergent,Detergent Pod,Detergent Pod, Laundry,Detergent Pods, Laundry,Detergent, Synthetic,Detergents, Synthetic,Laundry Detergent Pod,Laundry Pod,Pod, Detergent,Pod, Laundry,Pod, Laundry Detergent,Pods, Detergent,Pods, Laundry,Pods, Laundry Detergent,Synthetic Detergents
D005453 Fluorescence The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis.
D000327 Adsorption The adhesion of gases, liquids, or dissolved solids onto a surface. It includes adsorptive phenomena of bacteria and viruses onto surfaces as well. ABSORPTION into the substance may follow but not necessarily. Adsorptions
D000779 Anesthetics, Local Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate. Anesthetics, Conduction-Blocking,Conduction-Blocking Anesthetics,Local Anesthetic,Anesthetics, Topical,Anesthetic, Local,Anesthetics, Conduction Blocking,Conduction Blocking Anesthetics,Local Anesthetics,Topical Anesthetics

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