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  "notes": "The slide uses a scientific table to challenge the 'no appreciable binding' claim found in a drug's package insert, citing reproducibility concerns regarding the source of that claim.",
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      "text": "We note that the package insert says that the drug \"has no appreciable binding to other histamine receptors,\" but the only source appears to be a 2006 preclinical paper by Bioprojet scientist Xavier Ligneau, a member of Schwartz’s inner circle and whose work other scientists have stated is not reproducible in their labs, leading us to take his papers with a grain of salt.",
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      "text": "Compared pharmacology of human histamine H3 and H4 receptors: structure–activity relationships of histamine derivatives",
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      "text": "3 The inhibition of [3H]histamine binding by two agonists, a protean agonist and five antagonists/inverse agonists confirms that the potency of many H3R ligands is retained or only slightly reduced at the H4R.",
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      "text": "The second paper on the previous slide is by a key scientist in the field, who in 1983 was the first to pharmacologically identify the H3 receptor. He tested a number of compounds (including Bioprojet’s) that target the H3 receptor and showed that they are also generally potent at the H4 receptor, as displayed in the table. He did not test pitolisant. We note that the package insert says that the drug “has no appreciable binding to other histamine receptors,” but the only source appears to be a 2006 preclinical paper by Bioprojet scientist Xavier Ligneau, a member of Schwartz’s inner circle and whose work other scientists have stated is not reproducible in their labs, leading us to take his papers with a grain of salt.",
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      "text": "“has no appreciable binding to other histamine receptors,” — Harmony Biosciences package insert",
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      "text": "Source: https://pubmed.ncbi.nlm.nih.gov/26939881/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751501/pdf/147-0706666a.pdf",
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      "text": "Table 1 Compared potencies of H3-receptor ligands at the human H4 and H3 receptors (H4Rs and H3Rs)",
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      "text": "Paper on off-target effects of H3 receptor drugs on the H4 receptor",
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