title: NMDA receptor dependent and independent components of veratridine toxicity in cultured cerebellar neurons are prevented by nanomolar concentrations of terfenadine.
abstract: Exposure of cultured neurons to nanomolar concentrations of terfenadine prevented the NMDA receptor-mediated early appearance (30min.) of toxicity signs induced by the voltage sensitive sodium channel activator veratridine. Terfenadine also provided an histamine-insensitive protection against delayed neurotoxicity by veratridine (24h), occurring independently of NMDA receptor activation, while not protecting from excitotoxicity following direct exposure of neurons to glutamate. Terfenadine reduced tetrodotoxin-sensitive inward currents, and reduced intracellular cGMP formation following veratridine exposure. Our data suggest that nanomolar concentrations of TEF may reduce excitatory aminoacid release following neuronal depolarization via a presynaptic mechanism involving voltage sensitive sodium channels, and therefore may be considered as a prototype for therapeutic drugs in the treatment of diseases that involve excitatory aminoacid neurotransmission.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oviedo, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Díaz-Trelles
authors.forename: A
authors.initials: A
authors.lastname: Novelli
authors.forename: G
authors.initials: G
authors.lastname: Puia
authors.forename: M
authors.initials: M
authors.lastname: Baraldi
authors.forename: M T
authors.initials: MT
authors.lastname: Fernández-Sánchez
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D062687:Sodium Channel Agonists; D016593:Terfenadine / Q000494:pharmacology*; D014701:Veratridine / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D062687:Sodium Channel Agonists; D014701:Veratridine; D016593:Terfenadine