How Do Melatonin Receptor Agonists Work?

Melatonin receptor agonists are medications prescribed to induce sleep and regulate the circadian rhythm. Circadian rhythm is the internal biological process that regulates the sleep-wake cycle to synchronize with the day and night cycle. Melatonin receptor agonists work by enhancing the activity of melatonin receptors.

Melatonin is a hormone produced by the pineal gland located deep in the center of the brain. The pineal gland receives information from the retina about the environment’s light-dark status and uses it to secrete melatonin during the dark phase.

Melatonin performs several essential functions in the body but is best known for the role it plays in promoting sleep during the night and regulating the sleep-wake cycle. Melatonin receptors are protein molecules on cell surfaces that initiate action when stimulated by melatonin and are found throughout the body.

Melatonin receptor agonists regulate the sleep-wake cycle by stimulating melatonin receptors MT1 and MT2 in the suprachiasmatic nucleus, a structure in the hypothalamus region of the brain that acts as the pacemaker for circadian rhythm. Stimulation of MT1 receptors induces sleep and MT2 receptors regulate the circadian rhythm.

Melatonin receptor agonists are administered as oral tablets, capsules, or suspensions to treat the following conditions:

• Insomnia: Sleep disorder that makes it difficult to fall asleep and stay asleep.
• Non-24-hour sleep-wake disorder: A circadian rhythm sleep disorder in which a person’s biological clock fails to synchronize with the 24-hour day and night cycle, more common in completely blind people who are unable to perceive light.
• Smith-Magenis syndrome: A rare genetic disorder that causes many cognitive and behavioral abnormalities, including sleep disturbances. 

Side effects of melatonin receptor agonists may include the following:

• Dizziness
• Somnolence (drowsiness)
• Fatigue
• Headache
• Dysgeusia (taste disorder)
• Nausea
• Increased level of liver enzyme alanine aminotransferase (ALT)
• Upper respiratory infections
• Urinary tract infections
• Nightmares and abnormal dreams
• Nighttime sleep disturbances in Smith-Magenis syndrome
• Depression
• Worsening of insomnia
• Hallucinations
• Mania
• Angioedema (swelling in the tissue under the skin or mucous membranes), rarely

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 melatonin receptor agonist drugs include:

• Hetlioz
• Hetlioz LQ
• ramelteon
• Rozerem
• tasimelteon