Asunto(s)
Humanos , Anestésicos Generales/farmacocinética , Canales Iónicos , Membranas/efectos de los fármacos , Canales de Calcio/efectos de los fármacos , Ácido gamma-Aminobutírico/efectos de los fármacos , Canales de Potasio/efectos de los fármacos , Receptores Nicotínicos , Receptores de Glutamato/efectos de los fármacos , Receptores de Glicina/efectos de los fármacos , Canales de Sodio/efectos de los fármacosRESUMEN
Local anesthesia is achieved by the binding of anesthetic molecules to the sodium channel, a membrane protein responsible for the transport of the extracellular sodium to the cytosol. Local anesthetics (LA) bind to the sodium channel inhibiting sodium transport and, as a consequence, the action potential responsible for the nervous impulse. Most LA are relatively hydrophobic ionizable amines that undergo partitioning into lipid. Both activity and toxicity correlate positively with LA hydrophobicity. Effects of LA on the structural and dynamical properties of the membranes lipid region may be responsible for some of the toxic effects caused by these molecules. The present review focuses on research done on the interaction between both the charged and uncharged forms of LA and lipid systems - bilayers and micelles. LA have been found to alter phospholipid gel to liquid crystal phase transition temperature (Tc), to affect bilayer permeability, to influence molecular packing, and to inhibit the bilayer to hexagonal phase transition. Anesthetics in micellized form disrupt bilayers giving rise to lipid-LA mixed micelle-like aggregates. The question of LA location in the bilayer is also addressed. Special emphasis is placed on work focusing on the quantitative analysis of drug binding, as well as on the effects of binding on physicochemical properties of the LA, such as extent of ionization (pK shifts) and rates of chemical reactions. The understanding of these phenomena has contributed to the development of less toxic liposomal formulations capable of prolonging the duration of anesthesia.
Asunto(s)
Anestésicos Locales/química , Canales de Sodio/química , Lípidos de la Membrana/química , Bloqueo Nervioso , Fosfolípidos/química , Anestésicos Locales/farmacocinética , Anestésicos Locales/farmacología , Anestésicos Locales/toxicidad , Membrana Dobles de Lípidos/química , Espectroscopía de Resonancia por Spin del Electrón , Hidrólisis , Cinética , Membranas/química , Membranas/efectos de los fármacos , Membranas/metabolismo , Espectroscopía de Resonancia Magnética , SolubilidadRESUMEN
El etanol al igual que otros alcoholes puede actuar en las membranas biológicas fundamentalmente de 3 formas: 1). alterando la fluidez de las membranas, lo que indirectamente afectaría el funcionamiento de las proteínas como enzimas y canales;2)produciendo una deshidratación a nivel de las membranas;3)interactuando directamente con las proteínas de la membrana. Los efectos del etanol en las membranas biológicas podrían explicar en parte, los efectos generalizados del etanol