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  "documentTitle": "Harmony Biosciences (HRMY)",
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  "presentationDate": "2023-03-28 00:00:00",
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      "text": "The simplistic – and since disproven – theory behind Wakix is that anti-histamines can cause drowsiness, so a drug that increases histamine levels should increase wakefulness.",
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      "text": "Mechanism of action diagram showing Pitolisant binding to H3 receptors.",
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      "text": "1. Pitolisant blinds to presynaptic H3 autoreceptors... 2. Acting as an inverse agonist... 3. This increased histamine in the synapse... 4. Increased histamine binding at H1 receptors... 5. Increased firing of histamine neurons...",
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      "text": "Harmony’s schtick is that Wakix – a histamine H3 receptor antagonist/inverse agonist - is a “first-in-class molecule with a novel mechanism of action specifically designed to increase histamine signaling the brain by binding to H3 receptors.” Histamine involvement in immune and inflammatory responses is well known, but it also acts as a neurotransmitter. The simplistic – and since disproven – theory behind Wakix is that anti-histamines can cause drowsiness, so a drug that increases histamine levels should increase wakefulness. There are 4 known histamine receptors: H1 and H4 are involved in allergic responses, the former targeted by OTC anti-histamines; H2 modifies gastric reflux; and H3 is primarily expressed in the CNS. By purportedly binding to the H3 receptor, Wakix claims to block histamine from binding to it and thereby increasing its level.",
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      "text": "“first-in-class molecule with a novel mechanism of action specifically designed to increase histamine signaling the brain by binding to H3 receptors.” — Harmony Biosciences S-1",
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