What is a Dual Orexin Receptor Antagonist (DORA)?

From the Guidelines

A Dual Orexin Receptor Antagonist (DORA) is a type of medication that helps people sleep by blocking the orexin receptors in the brain, which are like the brain's "wake-up" buttons.

What is a DORA?

A DORA is a special kind of medicine that helps people who have trouble sleeping. It works by blocking the orexin receptors in the brain, which are responsible for keeping us awake.

How does it work?

These medications, such as suvorexant, lemborexant, and daridorexant, inhibit the action of orexin neuropeptides, promoting a good night's sleep.

Key points to know:

• DORAs are designed to treat insomnia by targeting the wake-promoting system in the brain 1.
• They have fewer side effects compared to traditional sleep medications, such as benzodiazepines, like morning grogginess or dependency issues 1.
• Common side effects may include headache, abnormal dreams, sleep paralysis, or mild hallucinations when falling asleep 1.
• Patients should take DORAs only when they can dedicate a full night (7-8 hours) to sleep and avoid alcohol consumption while using them.

Important considerations:

• DORAs, like suvorexant, have been shown to improve sleep quality and reduce symptoms of insomnia in clinical trials 1.
• However, it's essential to follow the recommended dosage and usage guidelines to minimize potential side effects and ensure safe use.
• As with any medication, it's crucial to consult with a healthcare professional before starting or stopping DORA treatment.

From the FDA Drug Label

The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive. Suvorexant binds to orexin receptors, OX1R and OX2R (Ki= 0.55 and 0. 35 nM, respectively).

A Dual Orexin Receptor Antagonist (DORA) is a type of medicine that helps people sleep by blocking the orexin receptors in the brain. Orexin is a chemical that helps keep us awake. When a DORA blocks the orexin receptors, it helps reduce the wakefulness signal, making it easier to fall asleep.

• Orexin receptors have two types: OX1R and OX2R.
• A DORA, like suvorexant, binds to both OX1R and OX2R receptors, which helps to suppress the wake drive 2.

From the Research

What is a Dual Orexin Receptor Antagonist (DORA)?

• A Dual Orexin Receptor Antagonist (DORA) is a type of medicine that helps people sleep by blocking the action of two chemicals in the brain called orexin A and orexin B 3, 4, 5.
• These chemicals are like messengers that tell the brain to stay awake, so when they are blocked, it's easier to fall asleep and stay asleep 5.
• DORAs are a new type of sleep medicine that is different from older medicines like benzodiazepines, which can be addictive and have other side effects 4, 6.

How do DORAs work?

• DORAs work by blocking the orexin receptors in the brain, which reduces the activity of the orexin chemicals and helps people fall asleep and stay asleep 3, 5.
• This can be especially helpful for people who have trouble sleeping due to insomnia, which is a common sleep disorder that can affect anyone 4, 6.
• DORAs have been shown to be effective in reducing the time it takes to fall asleep and increasing the amount of time spent sleeping, which can improve overall sleep quality and reduce daytime fatigue 3, 4.

Examples of DORAs

• Suvorexant (Belsomra) is an example of a DORA that has been approved by the US Food and Drug Administration (FDA) for the treatment of insomnia 3, 4.
• Daridorexant is another example of a DORA that has been recently approved for the treatment of insomnia and has shown promising results in clinical studies 6.
• Lemborexant is also a DORA that has been investigated as a treatment for insomnia comorbid with psychiatric disorders, such as depression and anxiety 7.

Benefits and limitations of DORAs

• DORAs have several benefits, including their ability to improve sleep quality and reduce daytime fatigue, with a lower risk of addiction and side effects compared to older sleep medicines 3, 4.
• However, DORAs may not be suitable for everyone, especially those with certain medical conditions, such as respiratory disease or obesity, and may interact with other medicines 4, 6.
• More research is needed to fully understand the benefits and limitations of DORAs and to determine their long-term safety and effectiveness 3, 4, 6, 7.