This moiety has successfully been used by several laboratories for the development of non-imidazole histamine H3 receptor antagonists and resulted in a number of highly potent and selective compounds, for example, JNJ-5207852 [24] and Pitolisant BF2.649 (Wakix) [25], the potent and selective H3R antagonist, which was approved by the European Medicine Agency (EMA) in March 2016 for the treatment of the orphan disease narcolepsy with and without cataplexy (Figure 1). This evidence concerns the gene HRH3 and narcolepsy.