Journal article
Antagonism of baclofen-induced antinociception by intrathecal administration of phaclofen or 2-hydroxy-saclofen, but not delta-aminovaleric acid in the rat
The Journal of pharmacology and experimental therapeutics, Vol.257(1), pp.360-368
04/1991
DOI: 10.1016/S0022-3565(25)24723-1
PMID: 1850472
Abstract
This study evaluated the ability of two new, selective antagonists of the gamma-aminobutyric acidB (GABAB) receptor, phaclofen (PHAC) and 2-hydroxy-saclofen (2-OH-S), to antagonize the increase in tail-flick latency (TFL) and hot-plate latency (HPL) produced by i.t. administered baclofen (BAC) in the rat. The putative GABAB receptor antagonist delta-aminovaleric acid (DAVA) was also examined for comparative purposes. Intrathecal (i.t.) pretreatment with increasing doses of PHAC (10-100 micrograms) shifted the dose-effect relationship of i.t. administered BAC progressively to the right in a parallel manner in both the tail-flick (TF) and hot-plate (HP) test. Schild analysis of the data yielded an apparent pA2 value of 7.3 +/- 0.1 and a slope of -0.98 +/- 0.14. By comparison, PHAC did not antagonize the increase in HPL produced by i.t. injection of the serotonin1A agonist, 8-hydroxy-N,N-dipropyl-2-aminotetralin. These observations indicate that PHAC competitively and selectively antagonizes BAC and further suggest that the antinociceptive effects of i.t. administered BAC are mediated by the PHAC-sensitive subtype of the GABAB receptor. Intrathecal injection of PHAC alone did not decrease TFL or HPL, suggesting that spinal GABAB receptors involved in nociception are not tonically activated. Although i.t. pretreatment with 2-OH-S (10-30 micrograms) also antagonized the antinociceptive effects of i.t. administered BAC, increasing doses of 2-OH-S did not produce progressive, rightward shifts in the dose-effect relationship of BAC. Indeed, i.t. administration of 2-OH-S alone modestly increased TFL, but not HPL in the rat. These observations suggest that 2-OH-S may be a partial agonist at spinal GABAB receptors.
Details
- Title: Subtitle
- Antagonism of baclofen-induced antinociception by intrathecal administration of phaclofen or 2-hydroxy-saclofen, but not delta-aminovaleric acid in the rat
- Creators
- S Aran - Department of Anesthesia and Critical Care, University of Chicago, IllinoisD L Hammond
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.257(1), pp.360-368
- Publisher
- United States
- DOI
- 10.1016/S0022-3565(25)24723-1
- PMID
- 1850472
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Grant note
- DA07004 / NIDA NIH HHS
- Language
- English
- Date published
- 04/1991
- Academic Unit
- Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984006421702771
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