Redox properties of local anesthetics: A structural determinant of closed channel blockers in BTX-modified Na+ channels.
Single channel analyses and macroscopic current measurements have shown that benzocaine is a predominantly closed channel blocker in BTX-modified Na+ channels; cocaine is an open channel blocker; and tetracaine, a dual channel blocker (Wang & Wang, 1994; Wang et al., 1994). The reason for such a selective state-dependent block by local anesthetics in BTX-modified Na+ channels is not clear. We assessed the redox properties of tetracaine, benzocaine, cocaine, and various derivatives by their ability to donate electrons to radical intermediates of eosin dye excited by visible light. Electron-donor properties of the drugs were previously proposed to be involved in Na+ channel blockade (Marinov, 1991). Our results provide evidence that redox properties of tetracaine, benzocaine, and their homologs correlate with their ability to enhance Na+ channel inactivation in BTX-modified Na+ channels. This correlation may be explained in terms of the previously proposed redox model of ion channels.
Marinov
B S
BS
Institute of Theoretical and Experimental Biophysics, Pushchino, Moscow Region, Russia.
Wang
G K
GK
D000779:Anesthetics, Local / Q000737:chemistry / Q000494:pharmacology; D001496:Batrachotoxins / Q000494:pharmacology; D001566:Benzocaine / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D003042:Cocaine / Q000737:chemistry* / Q000494:pharmacology; D004583:Electrons; D004801:Eosine Yellowish-(YS) / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006427:Hemin / Q000378:metabolism; D008024:Ligands; D008027:Light; D008954:Models, Biological; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D015222:Sodium Channels / Q000378:metabolism*; D013748:Tetracaine / Q000737:chemistry* / Q000494:pharmacology
D000779:Anesthetics, Local; D001496:Batrachotoxins; D005456:Fluorescent Dyes; D008024:Ligands; D015222:Sodium Channels; D013748:Tetracaine; D006427:Hemin; D003042:Cocaine; D004801:Eosine Yellowish-(YS); D001566:Benzocaine