title: Block of deltamethrin-modified sodium current in cultured mouse neuroblastoma cells: local anesthetics as potential antidotes.
abstract: Effects of local anesthetics and anticonvulsants on the pyrethroid-modified sodium current in cultured mouse neuroblastoma cells have been investigated using the suction pipette voltage clamp technique. In the presence of 10 microM of the pyrethroid deltamethrin the sodium current consists of an enhanced peak current during membrane depolarization and a slowly decaying, deltamethrin-induced tail current remaining after repolarization. At the onset of block the local anesthetics tetracaine, lidocaine and QX 314 reduced the deltamethrin-induced tail current more effectively than the peak current. Lidocaine, but not phenytoin, caused a time-dependent block of tail currents evoked by membrane depolarizations lasting 10-1000 ms. Both lidocaine- and phenytoin-induced blocks were independent of the membrane potential during the tail current. The anticonvulsants phenytoin, phenobarbital and valproate blocked the tail and the peak sodium current to the same extent, but diazepam, mephenesin and urethane blocked the peak current more effectively. Vitamin E, which suppresses pyrethroid-induced paresthesia of the skin, had no effect on the voltage-dependent sodium current. It is concluded that indirect effects of anticonvulsants on pyrethroid-induced toxic symptoms predominate, whereas local anesthetics preferentially block the pyrethroid-induced tail current. Therefore, local anesthetics are potentially useful pyrethroid antidotes.
authors.affiliation: Research Institute of Toxicology, University of Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Oortgiesen
authors.forename: R G
authors.initials: RG
authors.lastname: van Kleef
authors.forename: H P
authors.initials: HP
authors.lastname: Vijverberg
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004553:Electric Conductivity; D007306:Insecticides / Q000494:pharmacology*; D007700:Kinetics; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma; D009570:Nitriles; D011722:Pyrethrins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology*
chemical_list: D000779:Anesthetics, Local; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; C006072:QX-222; C012647:QX-314; C017180:decamethrin; D013779:Tetrodotoxin; D008012:Lidocaine