SITE OF ACTION AND ACTIVE FORM OF LOCAL ANESTHETICS

Abstract

Publisher Summary Local anesthetics penetrate the nerve membranes in the uncharged molecular forms, are dissociated into cations inside the axon, and exert the blocking action in the cationic forms from inside the nerve membrane. This chapter presents the interpretation of the existing data in the literature using the present model. The experimental data is described in a summarized form in the chapter and, the data is in support of the concept that local anesthetics block the action potential by combining with a site on the inside surface of the nerve membrane in their charged form. The effects of pH changes on the blocking potency of tertiary amine local anesthetics can be accounted for by this model. Moreover, quaternary amines are able to block the action potential much more strongly from inside than from outside the nerve membrane. The chapter discusses several factors that may affect the present analyses. These factors are the concentrations in the unstirred membrane layer, the possible dilution of local anesthetics, the possibility that both charged and uncharged forms of local anesthetics are active in blocking the action potential, and the possibility that the active sites on receptors in the nerve membrane are changed in their sensitivity to the local anesthetics when pH is altered because of titration of active groups. However, within the limit of pH change used in the study described in the chapter, the fourth factor that may affect the present analyses can be excluded for some reasons. The chapter highlights these reasons. The last factor that may affect these analyses is the penetration of certain quaternary compounds to the membrane.