JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aran, S.
Right arrow Articles by Hammond, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aran, S.
Right arrow Articles by Hammond, D. L.

Antagonism of baclofen-induced antinociception by intrathecal administration of phaclofen or 2-hydroxy-saclofen, but not delta- aminovaleric acid in the rat

S Aran and DL Hammond

Department of Anesthesia and Critical Care, University of Chicago, Illinois.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 257, Issue 1, pp. 360-368, 04/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
T. L. Yaksh
A Drug Has To Do What a Drug Has To Do
Anesth. Analg., November 1, 1999; 89(5): 1075 - 1075.
[Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics.