Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 49, 2019 - Issue 6
667
Views
9
CrossRef citations to date
0
Altmetric
Animal Pharmacokinetics and Metabolism

Disposition and metabolism of [14C]lemborexant, a novel dual orexin receptor antagonist, in rats and monkeys

ORCID Icon, &
Pages 688-697 | Received 13 Apr 2018, Accepted 26 May 2018, Published online: 05 Jul 2018

References

  • American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders, 5th ed. Arlington, VA: American Psychiatric Publishing.
  • Beuckmann CT, Sinton CM, Williams SC, et al. (2004). Expression of a poly-glutamine-ataxin-3 transgene in orexin neurons induces narcolepsy-cataplexy in the rat. J Neurosci 24:4469–77.
  • Beuckmann CT, Suzuki M, Ueno T, et al. (2017). In vitro and in silico characterization of lemborexant (E2006), a novel dual orexin receptor antagonist. J Pharmacol Exp Ther 362:287–95.
  • Brisbare-Roch C, Dingemanse J, Koberstein R, et al. (2007). Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med 13:150–5.
  • Chemelli RM, Willie JT, Sinton CM, et al. (1999). Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–51.
  • Hara J, Beuckmann CT, Nambu T, et al. (2001). Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30:345–54.
  • Murphy P, Moline M, Mayleben D, et al. (2017). Lemborexant, a dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med 13:1289–99.
  • Park BK, Kitteringham NR, O’Neill PM. (2001). Metabolism of fluorine-containing drugs. Annu Rev Pharmacol Toxicol 41:443–70.
  • Roth T, Coulouvrat C, Hajak G, et al. (2011). Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, Second Edition criteria: results from the America Insomnia Survey. Biol Psychiatry 69:592–600.
  • Sakurai T, Amemiya A, Ishii M, et al. (1998). Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–85.
  • Samuel K, Yin W, Stearns RA, et al. (2003). Addressing the metabolic activation potential of new leads in drug discovery: a case study using ion trap mass spectrometry and tritium labeling techniques. J Mass Spectrom 38:211–21.
  • Willie JT, Chemelli RM, Sinton CM, et al. (2003). Distinct narcolepsy syndromes in orexin receptor-2 and orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 38:715–30.
  • Yoshida Y, Naoe Y, Terauchi T, et al. (2015). Discovery of (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyrid-in-2-yl)cyclopropanecarboxamide (E2006): a potent and efficacious oral orexin receptor antagonist. J Med Chem 58:4648–64.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.