Interaction of Human Serum Proteins with Local Anesthetic Agents

Abstract

Investigations of cationic interactions with proteins have been relatively few as compared with the extensive studies done with organic anions. Recent work, however, has indicated that interactions with cations show some similarities as well as some major differences to interactions with anions.' Quantitative comparisons of binding ability by the equilibrium dialysis method have shown that, among ions of equal size, organic cationic dyes are bound much less than organic anionic dyes by plasma albumin.' On the other hand, Glassman2 has observed that long chain detergents form a stoichiometric complex with plasma albumin, in which the number of detergent molecules corresponds closely to the number of carboxyl groups on the protein.Examples of organic cations of considerable importance in the biological sciences are the group of synthetic agents commonly referred to as local anesthetics. As is well known, local anesthetics are drugs that in sufficient concentration are capable of blocking nerve conduction along both sensory and motor fibers. When carefully controlled concentration is used, it is possible to produce loss of sensation without motor paralysis because sensory fibers are always affected before motor fibers. Most local anesthetics, when used properly, can produce anesthesia in a ceratin definite portion of the body without producing a systemic effect. Some of the anesthetic agents exert not only a local action but also a central one. The synthetic agents, however, have slight effect on the central nervous system, and it was a select group of these agents that was chosen for this study of the interaction of these agents with blood-serum proteins.Various organic compounds are effective local anesthetic agents, and their usefulness in the treatment of patients has been demonstrated. On the other hand, certain limitations to the effectiveness of the drugs have resulted from unfavorable side effects that develop in some patients following increasing concentrations of the drugs. If these side effects, which become quite serious in some patients and result in necessary withdrawal of the drugs, could be eliminated, then the usefulness of the drugs could be greatly extended. The plasma proteins, by interacting with small organic ions and molecules, render them biologically inactive, thus decreasing the concentration of free drug and in turn reducing the toxic effects.3 Also, the interaction between local anesthetics and the plasma proteins would aid in the transport of the compounds from one

Crystallographic analysis reveals a unique lidocaine binding site on human serum albumin

“…Bailey and Briggs (2004) measured lidocaine by a homogeneous enzyme immunoassay, and from their data it is possible to calculate a K-value of 5.1 Â 10 2 M À1 , assuming binding to one site. In contrast to the present results and to the studies just cited, Sawinski and Rapp (1963) several years ago reported binding to two sites with the same and much higher K-value, namely 1.3 Â 10 5 M À1 . These authors quantified unbound lidocaine in an indirect way.…”

“…Thus, Sawinski and Rapp have reported binding to two sites with the same K-value (Sawinski and Rapp, 1963), whereas other studies have suggested low-affinity binding to only one site (Krauss et al, 1986;Bailey and Briggs, 2004). The present results are in accordance with the latter binding model.…”

A study on reducing the absorption of lidocaine from the airway in cats

“…The pharmacokinetic characteristics of gradual lidocaine application through the trachea are different from that of a single application 19 . The data from testing the bronchoscopic administration of drug showed that the plasma concentration of lidocaine depends on the total amount administered and the peak concentration values, which, in most patients, occurs between 5-30 minutes after drug delivery 20,21 .…”

“…The drug concentration of Group LG was lower than that of Group LS after 10 minutes of treatment ( Figure 1A). Taking into account the toxic effects, as far as plasmatic binding is concerned, some researches consider the gamma globulin as a second site of binding in serum for the lidocaine 19,20 , since it can diminish the free fraction of such drug, and, as a consequence, lead to a lesser adverse effect. However, in the current experiment, the heart rate and blood pressure decreased similarly in Group LS and in Group LG, something that was statistically different of what happened with Groups LE and C, showing what could be considered a limitation of our study.…”

Spectroscopic and voltammetric characterizations of the interaction of two local anesthetics with bovine serum albumin

“…Among these methods, the equilibrium dialysis and ultrafiltration are classical experimental methods. Sawinski and Rapp [1] used equilibrium dialysis to investigate the interaction of PCH or TCH with human serum albumin (HSA). Koizumi et al [2] used ultrafiltration and frontal analysis to determine the binding between procaine and HSA.…”