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Wake Up To FRESH Mornings

Mode Of Action1-3

DAYVIGO is a new dual orexin receptor antagonist (DORA) that targets the brain's wakefulness-regulating system.

The Role of Orexins In Sleep - Wake Regulation1-3

The orexin signaling system is a central promoter of wakefulness.

Normal Sleep-Wake Regulation

Daytime

Daytime

Daytime

In the daytime, orexins help us stay awake

Night

Night

Daytime

At night, orexin activity is low, letting us sleep

Normal Sleep-Wake regulation occurs when the wake-promoting pathway which is regulated by orexin and monoaminergic neurotransmitters like histamine, dopamine, etc. predominates during the day, and the sleep promoting pathway predominates regulated by melatonin, GABA, adenosine predominates at night.

Insomnia

Insomnia

Insomnia

Daytime

In insomnia, excess orexins prevent us sleeping

Dayvigo

Dayvigo

Daytime

DAYVIGO blocks orexin activity

In insomnia, patients have difficulty falling asleep or staying asleep as a result of an imbalance and conflict between wake promoting pathways and sleep promoting pathways.

What is Dayvigo

Brain
  • Orexin
    Orexin
  • Dayvigo
    Dayvigo
  • OX1R
    OX1R
  • OX2R
    OX2R
  • Orexin- producing neurons
    Orexin-producing neurons
  • Orexin neuron projections through the brain
    Orexin neuron projections through the brain
  • Major wake-controlling neurons expressing orexin receptors
    Major wake-controlling neurons expressing orexin receptors

DAYVIGO blocks orexin activity at night2

  • A Dual Orexin Receptor Antagonist (DORA) is thought to treat insomnia by blocking orexin signals in the brain that are believed to play a role in wakefulness.
  • Believed to help patients fall asleep and stay asleep during the night by blocking the orexin pathway—which is thought to suppress the wake drive
  • DAYVIGO, a DORA, did not interact in vitro* with most targets considered to be involved in sleep/wake regulation, including:
  • Binding sites for GABA and benzodiazepines on the GABAα receptor
  • Serotonin
  • Noradrenaline
  • Histamine
  • Acetylcholine
  • Dopamine
  • GABA=gamma aminobutyric acid. *Defined as <50% inhibition.

Mode Of Action1-3

Brain Video

Pharmacokinetics

Brain Video

The maximum concentration (Cmax) and Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24h) of Dayvigo increased with increasing dose. Cmax was 70.2 ng/mL, and plasma Dayvigo concentrations at 3 and 8 hours post dose were 31.4 ng/mL and 17.9 ng/mL, respectively, on Day 14 after administration of 10 mg.

The affinity of Dayvigo to the orexin receptors is high & dissociation these receptors is fast and it is a Competitive Reversible Antagonist at both OXR1 & OXR2 Receptors.

References:

  1. Dayvigo (Lemborexant) India Prescribing Information: 2021.
  2. Beuckmann CT, Suzuki M, Ueno T, Nagaoka K, Arai T, Higashiyama H. In Vitro and In Silico Characterization of Lemborexant (E2006), a Novel Dual Orexin Receptor Antagonist. J Pharmacol Exp Ther. 2017;362(2):287-95.
  3. Rosenberg R, Murphy P, Zammit G, et al. Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2019;2(12):e1918254.