Phaclofen antagonizes the antinociceptive but not the sedative effects of (-)-baclofen.

1. Intraperitoneal (ip) injection of (-)-baclofen induced long-lasting antinociceptive and sedative effects in rats. 2. Phaclofen, the phosphonic derivative of baclofen, fully antagonized the antinociceptive effect of (-)-baclofen. When injected intracerebroventricularly (icv), but not ip, phaclofen antagonized in a dose-dependent fashion (50-200 micrograms) the delays in behavioral response induced by (-)-baclofen (2.5-10 mg/kg ip) in both hot plate and tail flick tests. 3. In addition phaclofen (100 micrograms icv) counteracted the loss of the righting reflex induced by (-)-baclofen (7.5-15 mg/kg ip). 4. In contrast, phaclofen (100-200 micrograms icv) counteracted only in part the sedative effect of (-)-baclofen. In rats pretreated with the antagonist (200 micrograms icv), the electrocorticographic hypersynchrony due to (-)-baclofen (5 mg/kg ip) is replaced by a synchronized pattern associated with behavioral sedation. 5. These data are consistent with the reported antagonism by phaclofen on the effects of (-)-baclofen. They also seem to indicate that in rats phaclofen-sensitive GABA-B receptors play an important role in the analgesic effects of baclofen, but only a minor role in the sedative effects of this drug.