Why does route of administration fundamentally alter olanzapine's metabolic effects from harmful to protective?

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Oral olanzapine causes weight gain and steatosis while i.p. administration prevents these effects and increases energy expenditure. The mechanistic basis for this route-dependent metabolic switch contradicts assumptions about drug effects being dose-dependent rather than delivery-route dependent. Gap type: contradiction Source paper: Hypothalamic JNK1-hepatic fatty acid synthase axis mediates a metabolic rewiring that prevents hepatic steatosis in male mice treated with olanzapine via intraperitoneal: Additional effects of PTP1B inhibition. (None, None, PMID:37230004)

Priority: 0.78 Domain: neuropsychopharmacology Hypotheses: 0
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Landscape Summary: Why does route of administration fundamentally alter olanzapine's metabolic effects from harmful to protective? is a 0.78 priority gap in neuropsychopharmacology. It has 0 linked hypotheses with average composite score 0.000. Status: open.

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Colonna, Sevlever, et al. (TREM2 biology)

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Why does route of administration fundamentally alter olanzapine's metabolic effects from harmful to protective? — INVOKE-2 (completed)

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