Anesthetics effect on membrane structure

L.M. (Eds.), Drug and Anesthetic Effects on Membrane Structure and Function, Wiley-liss, NewYork 1991. 

Trudell J.R., in Drug and Anesthetic Effects on Membrane Structure and Function, R.C. Aloia, C.C. Curtain, L.M. Gordon (Eds.), Wiley-Iiss, New York 1991, pp. 1 13. 

Interaction of small molecules and ions with lipid bilayers is of importance from the point of view of membrane transport and other processes such as aaion of drugs and anesthetics on membranes. This includes a number of antibiotics and fatty acids also. The effect of these perturbations on the lipid bilayer in terms of differences in the structure and dynamics of the lipids close to the perturbative group versus the bulk lipids is also interesting and may... 

The toxicity of organic solvents or hydrophobic substances for microorganisms depends mainly on their effects on biological membranes - similar to membrane effects of several anesthetics. This concerns especially effects on cytoplasmatic membranes. The following main changes of membrane structures and functions have been observed ... 

Local anesthetics interact with peripheral nerve cell membranes and exert a pharmacological effect [34]. Potential oscillation was measured in the presence of 20 mM hydrochlorides of procaine, lidocaine, tetracaine, and dibucaine (structures shown in Fig. 16) [19]. Amplitude and the oscillatory and induction periods changed, the extent depending on the... 

Many substances of widely different chemical structure abolish the excitability of nerve fibers on local application in concentrations that do not cause permanent injury and that may not affect other tissues. Sensory nerve fibers are most susceptible, so that these agents produce a selective sensory paralysis, which is utilized especially to suppress the pain of surgical operation. This property was first discovered in cocaine, but because of its toxicity and addiction liability, it has been largely displaced by synthetic chemicals. The oldest of these, procaine (novocaine), is still the most widely used. Its relatively low toxicity renders it especially useful for injections, but it is not readily absorbed from intact mucous membranes and is therefore not very effective for them. Many of its chemical derivatives are also used. They differ in penetration, toxicity, irritation, and local injury as well as in duration of action and potency. Absolute potency is not so important for practical use as is its balance with the other qualities. If cocaine is absorbed in sufficient quantity, it produces complex systemic actions, involving stimulation and paralysis of various parts of the CNS. These are mainly of toxicological and scientific interest. Its continued use leads to the formation of a habit, resembling morphinism. This is not the case with the other local anesthetics. 

Based on the earlier work of Meyer and Overton, who showed that the narcotic effect of anesthetics was related to their oil/water partition coefficients, Hansch and his co-workers have demonstrated unequivocally the importance of hydrophobic parameters such as log P (where P is, usually, the octanol/water partition coefficient) in QSAR analysis.28 The so-called classical QSAR approach, pioneered by Hansch, involves stepwise multiple regression analysis (MRA) in the generation of activity correlations with structural descriptors, such as physicochemical parameters (log P, molar refractivity, etc.) or substituent constants such as ir, a, and Es (where these represent hydrophobic, electronic, and steric effects, respectively). The Hansch approach has been very successful in accurately predicting effects in many biological systems, some of which have been subsequently rationalized by inspection of the three-dimensional structures of receptor proteins.28 The use of log P (and its associated substituent parameter, tr) is very important in toxicity,29-32 as well as in other forms of bioactivity, because of the role of hydrophobicity in molecular transport across cell membranes and other biological barriers. 

A. blocker antihistamines are structurally related to histamine and antagonize the effects of histamine on H., receptor sites. They possess anticholinergic effects (except the nonsedating agents astemizole, azelastine, cetirizine, desloratadine, fexofenadine, loratadine, and terfenadine). They may also stimulate or depress the CNS, and some agents (eg, diphenhydramine) have local anesthetic and membrane-depressant effects in large doses. 

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