Format

Send to

Choose Destination
Neurosci Lett. 2000 Feb 18;280(2):107-10.

Inhibition of K(+)-evoked glutamate release from rat neocortical and hippocampal slices by gabapentin.

Author information

1
Department of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105, USA. david.dooley@wl.com

Abstract

Gabapentin (Neurontin((R))) has preclinical and clinical efficacy as an anticonvulsant, antihyperalgesic, anxiolytic, and neuroprotective drug. Since L-glutamic acid (GLU) is involved in various CNS (central nervous system) disorders, gabapentin may attenuate the release of this neurotransmitter possibly by interacting with the auxiliary alpha(2)delta subunit of voltage-sensitive calcium channels (VSCC). The effects of gabapentin, pregabalin (S-(+)-3-isobutylgaba) and its enantiomer R-(-)-3-isobutylgaba, and N- and P/Q-type VSCC-targeting peptide ligands (omega-conotoxin MVIIA, omega-conotoxin MVIIC, omega-agatoxin TK) were assessed in vitro on K(+)-evoked (endogenous) GLU release from rat neocortical and hippocampal slices. Gabapentin and pregabalin decreased GLU release by 11-26% with R-(-)-3-isobutylgaba being less effective than pregabalin. The reference N- and P/Q-type VSCC-targeting ligands reduced GLU release by 19-55% to implicate these VSCC in this Ca(2+)-dependent process. The inhibitory effect of gabapentin and related compounds on GLU release may reflect a subtle modulation of VSCC function which normalizes pathological changes in neurotransmitter release.

PMID:
10686389
DOI:
10.1016/s0304-3940(00)00769-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center