Using the hot plate test, the potency and mechanism of the analgesic activity of levonantradol was studied in mice. Levonantradol is 10 to 30 times more potent than morphine; the antinociception can be only partially blocked by naloxone. Similar limited antagonism by cholinergics indicates possible opiodergic mechanism. The role of serotoninergic pathways is unclear; antinociception is partially blocked by 5,7‐dihydroxytryptamine, unaffected by p‐chlorophenylalanine, and potentiated by cyproheptadine. Levonantradol blocks naloxone‐induced signs of abstinence in morphine‐dependent mice, being 3000 times more potent than morphine and 300 times more potent than Δ9‐tetrahydrocannabinol (THC).
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