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Mechanism of action: melanocortin cAMP/PKA/MITF cascade Presynaptic activation of cutaneous MC1R and central MC3R/MC4R/MC5R PRIMARY PATHWAY MELANOGENESIS MC1R on melanocytes High-affinity binding to the MC1R receptor on epidermal melanocytes

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Body-weight scaling is not straightforward: allometric differences in metabolism between a 2 kg rodent model and a 40 kg dog mean a simple g/kg extrapolation may not translate

Excessive APAP metabolism depletes glutathione and increases N-acetyl-p-benzoquinoneimide (NAPQI) levels, leading to oxidative stress, DNA damage, and cell necrosis in the liver, which in turn leads to liver damage

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