Nonclinical evaluation of abuse liability of the dual orexin receptor antagonist lemborexant.

@article{Asakura2021NonclinicalEO,
  title={Nonclinical evaluation of abuse liability of the dual orexin receptor antagonist lemborexant.},
  author={Sho Asakura and Motohiro Shiotani and David V. Gauvin and Atsushi Fujiwara and Takashi Ueno and Nancy Bower and Carsten Theodor Beuckmann and Margaret Moline},
  journal={Regulatory toxicology and pharmacology : RTP},
  year={2021},
  pages={
          105053
        }
}
1 Citations

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TLDR
The overall incidence of abuse-related adverse events, such as euphoric mood and hallucination, was numerically lower with suvorexant than zolpidem, suggesting that the overall abuse liability of suvorxant may be lower than zOLpidem.

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TLDR
The withdrawal, discriminative stimulus effects and tolerance shown with zolpidem were similar to those shown previously with benzodiazepines under similar conditions.

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TLDR
Neither spontaneous nor flumazenil-induced precipitated withdrawal was observed in zolpidem-treated mice, and there was no change in its ability to produce sedative and anticonvulsant effects.

The dual orexin receptor antagonist almorexant, alone and in combination with morphine, cocaine and amphetamine, on conditioned place preference and locomotor sensitization in the rat.

TLDR
The findings suggest that almorexant itself does not exert conditioned rewarding effects in the rat and that it may acutely interfere with the expression of CPP or locomotor sensitization in a drug-dependent manner (monoaminergic psychostimulants vs. opiates).

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TLDR
It was found that subchronic treatment of zolpidem and diazepam induced distinct but overlapping GABAAR subunit mRNA changes in the cortex but fewChanges in the hippocampus, amygdala, or prefrontal cortex, and subunit-specific mRNA changes.

Preclinical in vivo characterization of lemborexant (E2006), a novel dual orexin receptor antagonist for sleep/wake regulation

TLDR
Results supported further clinical evaluation of lemborexant as a potential candidate for treating insomnia and other sleep disorders and demonstrated inhibition of the orexin signaling pathway.