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Histamine H3 Receptor Pharmacophores in Promising Multi-target Directed Ligands

Abstract: The classic “magic bullet” of Paul Ehrlich follows the rule: one disease – one reason – one drug. Modern therapeutic approaches have detected a number of different diseases caused by numerous effects as well as different targets for the same disease [1]. This is especially true for neurological and neurodegenerative diseases. Based on the therapeutic profile of the first marketed histamine H3 receptor antagonist pitolisant (approved as orphan drug for narcolepsy), numerous approaches in dual- or multi-targeting have been developed to combine more than one pharmacophore or bring a beneficial therapeutic profile in one drug [2]. A selection of rational multi-targeting approaches based on histamine H3 receptor ligands for the polypharmacological design will be shown with stories of success, but also with failures.

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