Add time:08/26/2019         Source:sciencedirect.com

1. Intraperitoneal (ip) injection of (−)-baclofen induced long-lasting antinociceptive and sedative effects in rats.2. PHACLOFEN (cas 114012-12-3), the phosphonic derivative of baclofen, fully antagonized the antinociceptive effect of (−)-baclofen. when injected intracerebroven-tricularly (icv), but not ip, phaclofen antagonized in a dose-dependent fashion (50–500 μg) 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 μg icv) counteracted the loss of the righting reflex induced by (−)-baclofen (7.5–15 mg/kg ip).4. In contrast, phaclofen (100–200 μg icv) counteracted only in part the sedative effect of (−)-baclofen. In rats pretreated with the antagonist (200 μg 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.

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