Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons.
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.
Rock
D M
DM
Pharmacology Department, Parke-Davis Research, Ann Arbor, MI 48106-1047.
Kelly
K M
KM
Macdonald
R L
RL
D000085:Acetates / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D003509:Cyclohexanecarboxylic Acids; D005333:Fetus; D000077206:Gabapentin; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D005971:Glutamates; D007473:Ion Channels; D015222:Sodium Channels; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D000077206:Gabapentin; D005998:Glycine