D-baclofen: Is it an antagonist at baclofen receptors?

1. 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-baclofeu. 2. 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. 3. 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. 4. 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 stereoselectlve baclofen receptors in a variety of pharmacological processes.