Nonclinical evaluation of abuse liability of the dual orexin receptor antagonist lemborexant - PubMed
Nonclinical evaluation of abuse liability of the dual orexin receptor antagonist lemborexant
Shoji Asakura et al. Regul Toxicol Pharmacol. 2021 Dec.
Free article
Abstract
Lemborexant is a dual orexin receptor antagonist (DORA) approved in multiple countries including the United States, Japan, Canada and Australia for the treatment of adults with insomnia. As required for marketing approval of new compounds with central nervous system activity with sedating effects, the abuse potential of lemborexant was assessed in accordance with regulatory guidelines, which included three nonclinical studies. These assessments comprised physical dependence and drug discrimination studies in rats and a self-administration study in rhesus monkeys. There was no evidence of withdrawal signs following abrupt drug discontinuation, indicating that lemborexant does not induce physical dependence. In the drug discrimination study, lemborexant at doses up to 1000 mg/kg administered orally did not cross-generalize to the zolpidem training stimulus, although another DORA included in the same experiment, suvorexant, showed partial generalization with zolpidem. In rhesus monkeys, lemborexant treatment did not induce any gross behavioral changes, and there was no increase in self-administration rates compared with control, indicative of a lack of reinforcing effects of lemborexant. Collectively, these nonclinical studies support the position that lemborexant, which has been placed in Schedule IV by the United States Drug Enforcement Administration, has a low risk of abuse in humans.
Keywords: Abuse potential; Drug dependence; Drug discrimination; Insomnia; Lemborexant; Orexin receptor antagonist; Physical dependence; Self-administration.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Similar articles
-
Moline M, Asakura S, Beuckman C, Landry I, Setnik B, Ashworth J, Henningfield JE. Moline M, et al. Psychopharmacology (Berl). 2023 Apr;240(4):699-711. doi: 10.1007/s00213-023-06320-y. Epub 2023 Feb 7. Psychopharmacology (Berl). 2023. PMID: 36749354 Free PMC article. Review.
-
Preclinical assessment of the abuse potential of the orexin receptor antagonist, suvorexant.
Born S, Gauvin DV, Mukherjee S, Briscoe R. Born S, et al. Regul Toxicol Pharmacol. 2017 Jun;86:181-192. doi: 10.1016/j.yrtph.2017.03.006. Epub 2017 Mar 6. Regul Toxicol Pharmacol. 2017. PMID: 28279667
-
Beuckmann CT, Ueno T, Nakagawa M, Suzuki M, Akasofu S. Beuckmann CT, et al. Sleep. 2019 Jun 11;42(6):zsz076. doi: 10.1093/sleep/zsz076. Sleep. 2019. PMID: 30923834 Free PMC article.
-
Landry I, Hall N, Aluri J, Filippov G, Reyderman L, Setnik B, Henningfield J, Moline M. Landry I, et al. J Clin Psychopharmacol. 2022 Jul-Aug 01;42(4):365-373. doi: 10.1097/JCP.0000000000001561. Epub 2022 Jun 24. J Clin Psychopharmacol. 2022. PMID: 35749758 Free PMC article. Clinical Trial.
-
Keks NA, Hope J. Keks NA, et al. Australas Psychiatry. 2022 Aug;30(4):530-532. doi: 10.1177/10398562221092310. Epub 2022 May 1. Australas Psychiatry. 2022. PMID: 35491942 Review.
Cited by
-
Abuse potential assessment of the dual orexin receptor antagonist daridorexant in rats.
Steiner MA, Toeroek-Schafroth M, Giusepponi ME, Dacome L, Tessari M. Steiner MA, et al. J Psychopharmacol. 2023 Dec;37(12):1249-1260. doi: 10.1177/02698811231215415. Epub 2023 Dec 7. J Psychopharmacol. 2023. PMID: 38059356 Free PMC article.
-
Moline M, Asakura S, Beuckman C, Landry I, Setnik B, Ashworth J, Henningfield JE. Moline M, et al. Psychopharmacology (Berl). 2023 Apr;240(4):699-711. doi: 10.1007/s00213-023-06320-y. Epub 2023 Feb 7. Psychopharmacology (Berl). 2023. PMID: 36749354 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials