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Orexin discovery

The whole field of research can reasonably be described as being revolutionized over a few years at the turn of the century through the discovery of two neuropeptide transmitters produced by cells of the hypothalamus. These hypocretins (Hcrt-1 and Hcrt-2), which are also known as orexins, are clearly the key to understanding narcolepsy, and a good deal of the normal sleep mechanism. The familial canine narcolepsy cases are associated with genetic mutations of this system, mice with targeted deletions of the gene for the precursor of these peptides display symptoms of narcolepsy, and the majority of humans with narcolepsy and the associated HLA characteristics have no detectable hypocretins in their cerebrospinal fluid. [Pg.113]

In summary, suvorexant (1) is the first and currently the only dual orexin antagonist to reach the market. This represents the first mechanistically novel insomnia treatment since ramelteon (6). The discovery route produced suvorexant in 12% overall yield with nine steps in the longest linear sequence. The manufacturing route produced suvorexant in 19% overall yield and five steps in the longest linear sequence, although further optimization strategies subsequently improved upon specific steps in this route also. [Pg.239]


See other pages where Orexin discovery is mentioned: [Pg.385]    [Pg.25]    [Pg.389]    [Pg.402]    [Pg.424]    [Pg.65]    [Pg.44]    [Pg.45]    [Pg.48]    [Pg.34]    [Pg.3122]    [Pg.193]    [Pg.255]    [Pg.872]    [Pg.111]    [Pg.114]    [Pg.369]    [Pg.947]    [Pg.243]    [Pg.226]    [Pg.1208]   
See also in sourсe #XX -- [ Pg.38 ]




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Orexins

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