D-Baclofen: is it an antagonist at baclofen receptors?
Following intrathecal administration into the spinal subarachnoid space, baclofen produced dose related increases in tail flick latency. L-Baclofen was twice as potent as the DL-racemate and 100 times more potent than D-baclofen. When D-baclofen was injected intrathecally 15 min prior to L-baclofen, the subsequent effect of L-baclofen was markedly reduced. This reduction was dose-related for D-baclofen in doses at least 20 times the L-baclofen dose. D-baclofen administered concomitantly with L-baclofen only slightly increased the effect of L-baclofen. Pretreatment with D-baclofen (up to 10 times the dose of L-baclofen) did not inhibit the effect of L-baclofen when drugs were injected intraperitoneally. These results indicate that D-baclofen can antagonize the antinociceptive effect of L-baclofen following intrathecal administration. D-Baclofen should prove to be a useful tool for investigation of the role of stereoselective baclofen receptors in a variety of pharmacological processes.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D018080:Receptors, GABA-B; D013237:Stereoisomerism
D000700:Analgesics; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D001418:Baclofen