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In the VMH, MORs hyperpolarize neurons to reduce cellular excitability, including those that express the leptin receptor, via enhancing GIRK currents (Emmerson and Miller, 1999)

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Other pharmacological options include catechol-O-methyltransferase (COMT) inhibitors like entacapone and opicapone, which extend the half-life of levodopa, do not cross the BBB at all and primarily affect peripheral metabolism, providing no direct action in the brain 59