title: Acute modulation of calcium currents and synaptic transmission by gabapentinoids.
abstract: Gabapentin and pregabalin are anticonvulsant drugs that are extensively used for the treatment of several neurological and psychiatric disorders. Gabapentinoids (GBPs) are known to have a high affinity binding to α2δ-1 and α2δ-2 auxiliary subunit of specific voltage-gated calcium channels. Despite the confusing effects reported on Ca (2+) currents, most of the studies showed that GBPs reduced release of various neurotransmitters from synapses in several neuronal tissues. We showed that acute in vitro application of pregabalin can reduce in a dose dependent manner synaptic transmission in both neuromuscular junctions and calyx of Held-MNTB excitatory synapses. Furthermore presynaptic Ca (2+) currents treated with pregabalin are reduced in amplitude, do not show inactivation at a clinically relevant low concentration of 100 μM and activate and deactivate faster. These results suggest novel modulatory role of acute pregabalin that might contribute to better understanding its anticonvulsant/analgesic clinical effects.
authors.affiliation: Instituto de Fisiología, Biología molecular y Neurociencias, UBA-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Osvaldo D
authors.initials: OD
authors.lastname: Uchitel
authors.forename: Mariano N
authors.initials: MN
authors.lastname: Di Guilmi
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Urbano
authors.forename: Carlota
authors.initials: C
authors.lastname: Gonzalez-Inchauspe
mesh_terms: D000588:Amines / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000077206:Gabapentin; D006801:Humans; D007700:Kinetics; D008024:Ligands; D000069583:Pregabalin; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D055366:Synaptic Potentials; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000588:Amines; D000927:Anticonvulsants; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D008024:Ligands; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin