title: Interaction of topiramate with glycine receptor channels.
abstract: Glycine receptor channels are pentameric ligand-gated ion channels that respond to the application of inhibitory neurotransmitters by opening of a chloride-selective central pore. Topiramate (TPM) is a broad-spectrum antiepileptic drug used as add-on or monotherapy for focal seizures. In the present study the interaction of TPM with glycine receptor channels was studied on outside-out patches from HEK293 cells expressing alpha1beta glycine receptor channels. The patch clamp techniques combined with ultra fast solution exchange enabled us to investigate the kinetics of receptor channels in presence of TPM. Our study showed no agonistic or potentiating effect for TPM on glycine receptor channels. However, in presence of 1 mM glycine + 1 mM TPM, the desensitization got faster and the peak current amplitude decreased. After the end of glycine + TPM pulses, off-currents occurred, suggestive for a specific channel block mechanism.
authors.affiliation: Department of Neurology, Medical University Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. mohammadi.bahram@mh-hannover.de
authors.forename: Bahram
authors.initials: B
authors.lastname: Mohammadi
authors.forename: Klaus
authors.initials: K
authors.lastname: Krampfl
authors.forename: Cener
authors.initials: C
authors.lastname: Cetinkaya
authors.forename: Heiner
authors.initials: H
authors.lastname: Wolfes
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.forename: Johannes
authors.initials: J
authors.lastname: Bufler
mesh_terms: D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D018009:Receptors, Glycine / Q000378:metabolism*; D000077236:Topiramate
chemical_list: D007473:Ion Channels; D018009:Receptors, Glycine; D000077236:Topiramate; D005632:Fructose; D005998:Glycine