Sean D Donevan

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1. The direct activation of the GABAA receptor by pentobarbitone (PB) and phenobarbitone (PHB) was characterized in cultured rat hippocampal neurons using whole-cell voltage clamp and single channel recording techniques. 2. In whole-cell recordings, PB and PHB produced a concentration-dependent activation of Cl- current (EC50 values, 0.33 and 3.0 mM,(More)
The term 'Ca2+ channel alpha2delta ligands' has recently been applied to an evolving drug class that includes gabapentin (Neurontin) and pregabalin (Lyrica), and reflects significant progress over the past decade in elucidating the mechanism of action of these drugs: a novel, specific action at one of the subunits constituting voltage-sensitive Ca2+(More)
In whole-cell voltage-clamp recordings from cultured rat hippocampal neurons, the 2,3-benzodiazepine GYKI 52466 was a potent antagonist of kainate- and AMPA-activated currents (IC50 values, 7.5 and 11 microM, respectively), but was inactive against N-methyl-D-aspartate (NMDA) or gamma-aminobutyric acid responses. The block produced by GYKI 52466 occurred in(More)
Conantokin G (Con G) is a 17-amino-acid peptide antagonist of N-methyl-D-aspartate (NMDA) receptors isolated from the venom of the marine cone snail, Conus geographus. The mechanism of action of Con G has not been well defined; both competitive and noncompetitive interactions with the NMDA-binding site have been proposed. In this study the mechanism of(More)
Felbamate is a promising new antiepileptic drug whose mechanism of action is unknown. In whole-cell voltage clamp recordings from cultured rat hippocampal neurons, clinically relevant concentrations of felbamate (0.1-3 mM) inhibited N-methyl-D-aspartate (NMDA) responses and potentiated gamma-aminobutyric acid (GABA) responses. Single-channel recordings(More)
Felbamate and meprobamate are structurally related propanediol dicarbamates that possess distinct pharmacological profiles. Felbamate is a minimally sedative, broad-spectrum anticonvulsant, whereas meprobamate is a strong sedative-anxiolytic agent. Previously, we reported that felbamate potentiates gamma-aminobutyric acid(A) (GABA(A)) receptor Cl- currents(More)
The anticonvulsant felbamate may act as an N-methyl-D-aspartate (NMDA) receptor antagonist, but the mechanism of block has not been fully characterized. We sought to identify the sites at which felbamate exerts its NMDA receptor blocking action using radioligand binding to rat forebrain membranes and whole-cell voltage clamp and single-channel recordings(More)
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that lack the glutamate receptor GluR2 subunit are Ca(2+)-permeable and exhibit inwardly rectifying current responses to kainate and AMPA. A proportion of cultured rat hippocampal neurons show similar Ca(2+)-permeable inwardly rectifying AMPA receptor currents. Inward rectification in(More)
The anticonvulsant activities of a noncompetitive (GYKI 52466) and a competitive (NBQX) AMPA/kainate antagonist were compared in the maximal electroshock (MES) seizure test and various chemoconvulsant models. Both antagonists were protective in the MES and pentylenetetrazol tests. GYKI 52466 was also protective against seizures and lethality induced by(More)
1. Neurons in the brainstem auditory pathway exhibit a number of specializations for transmitting signals reliably at high rates, notably synaptic AMPA receptors with very rapid kinetics. Previous work has not revealed a common structural pattern shared by the AMPA receptors of auditory neurons that could account for their distinct functional properties. 2.(More)