Does gabapentin act as an agonist at native GABAB receptors?
Journal
Journal of Biomedical Science
Journal Volume
11
Journal Issue
3
Date Issued
2004
Author(s)
Abstract
Gabapentin, a novel anticonvulsant and analgesic, is a γ- aminobutyric acid (GABA) analogue but was shown initially to have little affinity at GABAA or GABAB receptors. It was recently reported to be a selective agonist at GABAB receptors containing GABAB1a-GABAB2 heterodimers, although several subsequent studies disproved that conclusion. In the present study, we examined whether gabapentin is an agonist at native GABAB receptors using a rat model of postoperative pain in vivo and periaqueductal gray (PAG) slices in vitro; PAG contains GABAB receptors, and their activation results in antinociception. An intrathecal injection of gabapentin or baclofen, a GABA B receptor agonist, induced antiallodynia in this postoperative pain model. Intrathecal injection of GABAB receptor antagonists CGP 35348 and CGP 55845 antagonized baclofen- but not gabapentin-induced antiallodynia. In ventrolateral PAG neurons, baclofen activated G-protein-coupled inwardly rectifying K+ (GIRK) channels in a manner blocked by CGP 35348 or CGP 55845. However, gabapentin displayed no effect on the membrane current. In neurons unaffected by gabapentin, baclofen activated GIRK channels through GABAB receptors. It is concluded that gabapentin is not an agonist at GABAB receptors that are functional in baclofen-induced antiallodynia in the postoperative pain model in vivo and in GIRK channel activation in ventrolateral PAG neurons in vitro. Copyright © 2004 National Science Council, ROC and S. Karger AG, Basel.
SDGs
Type
journal article