“…Asahi et al found that replacement of alanine and leucine in sites 11 and 15 in orexin‐B increased its affinity to its receptors and induced Ca 2+ elevation in CHO cells . On the other hand, since the first OX 2 receptor inhibitor, N‐Acyl 6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline, was developed by Masaaki et al., lots of researchers tried hard to explore nonpeptide antagonists of OX 2 receptors, such as substituted 4‐phenyl‐[1,3]dioxanes series, (3,4‐dimethoxyphenoxy)alkylamino acetamides, N ‐ethyl‐2‐[(6‐methoxy‐pyridin‐3‐yl)‐(toluene‐2‐sulphonyl)‐amino]‐ N ‐pyridin‐3‐ylmethyl‐ acetamide (EMPA), 2‐methyl‐3‐furanyl‐4H‐1,2,4‐triazol‐3‐ylthioamides, benzoxazepine‐based compound 1a, spiropiperidine‐based compound 4f, and 2,5‐diarylnicotinamides . Moreover, administration of TCSOX229, antagonist of OX 2 receptor, elicited increase of REM sleep and reduced wakefulness .…”