Abstract
Gabapentin (GBP) is a cyclic gamma-aminobutyric acid (GABA) analog and investigational antiepileptic drug which is effective in the treatment of a variety of human and experimental seizures. GBP's antiepileptic mechanism of action is not known. The present studies tested for effects of GBP on inhibitory (GABA and glycine) and excitatory (N-methyl-D-aspartate (NMDA) and non-NMDA) amino acid neurotransmitter receptors, on repetitive firing of sodium (Na+) action potentials, and on voltage-dependent calcium (Ca2+) channel currents in cultured rodent neurons using intracellular, whole cell, or single channel recording techniques. GBP did not have a significant effect in any experiment when tested at or above concentrations that are therapeutic in humans except for a variable enhancement of NMDA-evoked depolarizations. These results suggest that the antiepileptic activity of GBP is not due to direct effects at receptors for inhibitory or excitatory amino acids or on voltage-dependent Na+ or Ca2+ channels.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetates / pharmacology*
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Action Potentials / drug effects
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Amines*
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Animals
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Anticonvulsants / pharmacology*
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Calcium Channels / drug effects
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Calcium Channels / physiology
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Cells, Cultured
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Cerebral Cortex / physiology*
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Cyclohexanecarboxylic Acids*
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Fetus
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Gabapentin
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Glutamates / pharmacology
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Glutamic Acid
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Glycine / pharmacology
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology
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Ion Channels / drug effects
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Ion Channels / physiology*
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Membrane Potentials / drug effects
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Mice
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N-Methylaspartate / pharmacology
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Neurons / drug effects
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Neurons / physiology*
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Neurons, Afferent / drug effects
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Neurons, Afferent / physiology*
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Nodose Ganglion / physiology*
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Rats
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Sodium Channels / drug effects
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Sodium Channels / physiology
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Spinal Cord / physiology*
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Synapses / drug effects
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Synapses / physiology
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gamma-Aminobutyric Acid / pharmacology
Substances
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Acetates
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Amines
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Anticonvulsants
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Calcium Channels
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Cyclohexanecarboxylic Acids
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Glutamates
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Ion Channels
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Sodium Channels
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Glutamic Acid
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gamma-Aminobutyric Acid
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N-Methylaspartate
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Gabapentin
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Glycine