Interaction of Human Serum Proteins with Local Anesthetic Agents

¹ Departments of Biochemistry, Physiology, and Pharmacology, Dental School, Loyola University, Chicago, Illinois

The interaction of human serum albumin and human serum gamma globulin with four local anesthetic agents, namely, procaine, butethamine, lidocaine, and mepivacaine, was studied. The method used was that of equilibrium dialysis in M/15 phosphate buffer of pH 7.0 at a temperature of 4° C. As far as statistical binding is concerned, serum albumin exhibited two binding sites for each of the four local anesthetics. On the other hand, no significant interaction occurred between gamma globulin and these agents. Also, since analyses of the data revealed that the order of magnitude of the intrinsic affinity constants of human serum albumin for procaine and butethamine is 10³, whereas for lidocaine and mepivacaine the order of magnitude is 10⁵, this means that, under the conditions of these experiments, the intrinsic affinity of human serum albumin for either procaine or butethamine is less than the corresponding affinity for either lidocaine or mepivacaine. Hence, on this basis, the anesthetic agents seemed to fall into two classes based on their binding ability, and these classes seemed to parallel the classes to which they belong with respect to their internal ester linkages (procaine and butethamine) or amide linkages (lidocaine and mepivacaine).