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Several compounds merit further optimization as potential non-addictive analgesics: mitraciliatine and isopaynantheine as mixed MOR antagonist/KOR agonist templates, and hKOR-selective N-oxide derivatives as partial agonists that may retain antinociceptive efficacy while mitigating the dysphoria and sedation associated with full KOR activation (Carlezon et al., 2006

A stall at 15 mg is a signal to reassess the overall approach, not to exceed the label

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PMID 3374544