How Do Orexin Antagonists Work?

Orexin antagonists are medications for treating insomnia. Orexin, also known as hypocretin, is a neurotransmitter secreted in the hypothalamus region of the brain. Neurotransmitters are substances that nerve cells (neurons) release to transmit signals to each other.

A cluster of orexin neurons in the hypothalamus synthesizes orexin, which is in two forms, orexin A and B. Orexin has vital functions such as regulation of sleep/wake states, energy expenditure, appetite, reward systems, mood and cognition. Orexin A and B bind to OX1 and OX2 receptors in orexin neurons to promote arousal and wakefulness.

Orexin receptors are particles on membranes of orexin neurons that initiate intracellular action to promote a state of wakefulness, when stimulated by orexin. Orexin antagonists bind to orexin receptors and block orexin from activating them, thus promoting sleep.

Orexin antagonists are oral tablets used for inducing and maintaining sleep in adults with insomnia.

Side effects of orexin antagonists may include the following:

• Somnolence (drowsiness)
• Fatigue
• Headache
• Sleep paralysis (temporary inability to move or speak, which typically occurs while falling asleep or upon waking)
• Nightmares or abnormal dreams
• Hypnagogic hallucinations (hallucinations that occur while falling asleep)
• Dizziness
• Cough
• Diarrhea
• Dry mouth
• Upper respiratory infection
• Palpitations
• Tachycardia (rapid heartbeat)
• Anxiety
• Psychomotor hyperactivity (restlessness with unintentional physical movements)
• Pruritus (itching)
• Nausea
• Vomiting

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of orexin antagonist drugs include:

• Belsomra
• daridorexant (pending FDA approval)
• Dayvigo
• lemborexant
• suvorexant