Actions of 4-amino-3-(5-methoxybenzo(b)furan-2-yl) butanoic acid and 4-amino-3-benzo(b)furan-2-yl butanoic acid in the rat spinal cord.
This study examined whether two putative GABAB receptor antagonists, 4-amino-3-(5-methoxybenzo (b)furan-2-yl) butanoic acid (MBFG) and 4-amino-3-benzo(b)furan-2-yl butanoic acid (BFG), antagonized the antinociception produced by intrathecal (i.t) administration of the GABAB receptor agonist baclofen in the rat. In rats pretreated with 30 micrograms i.t. MBFG, the dose-effect relationship of D,L-baclofen was shifted approximately 2-fold and 4-fold to the right in the tail flick and hot plate tests, respectively. No further shift was obtained in the presence of 60 micrograms i.t. MBFG. I.t. injection of MBFG by itself did not alter either tail flick or hot plate latency. These data suggest that MBFG is a GABAB receptor antagonist in the spinal cord in vivo, although of marginal utility. Contrary to expectations, i.t. administration of 30-60 micrograms BFG alone increased tail flick and hot plate latencies; this increase was partially attenuated by coadministration of the GABAB receptor antagonist phaclofen. Pretreatment with 10 micrograms i.t. BFG, which was itself without effect on nociceptive threshold, antagonized the antinociceptive effects of 0.3 microgram i.t. L-baclofen, but interacted with higher and lower doses of baclofen in a complex manner. These results suggest that BFG acts as weak, partial agonist at GABAB receptors and that it may have additional, non-specific effects in the spinal cord of the rat. The pharmacological properties of BFG, therefore, resemble those of the GABAB receptor partial agonist/antagonist beta-phenyl-GABA, to which it bears a strong structural resemblance.(ABSTRACT TRUNCATED AT 250 WORDS)
Hammond
D L
DL
Department of Anesthesia and Critical Care, University of Chicago, IL 60637.
Moy
M L
ML
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000700:Analgesics; D001572:Benzofurans; D058787:GABA-A Receptor Antagonists; C060686:4-amino-3-(5-methoxybenzo(b)furan-2-yl)butanoic acid; C079416:4-amino-3-benzo(b)furan-2-ylbutanoic acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen