Last reviewed 2026-04-20 · How we verify

Rozerem (RAMELTEON)

Rozerem works by activating the melatonin receptor type 1A to regulate sleep-wake cycles.

Rozerem (Ramelteon) is a melatonin receptor type 1A agonist, a small molecule drug developed by Takeda Pharms USA. It was approved by the FDA in 2005 for the treatment of initial insomnia. Rozerem works by targeting the melatonin receptor type 1A, mimicking the action of the natural hormone melatonin to regulate sleep-wake cycles. The drug is now off-patent, with multiple generic manufacturers available. Key safety considerations include its short half-life and low bioavailability.

At a glance

Mechanism of action

Ramelteon is melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and relative selectivity over the MT3 receptor.The activity of ramelteon at the MT1 and MT2 receptors is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle.Ramelteon has no appreciable affinity for the GABA receptor complex or for receptors that bind neuropeptides, cytokines, serotonin, dopamine, noradrenaline, acetylcholine, and opiates. Ramelteon also does not interfere with the activity of number of selected enzymes in standard panel.The major metabolite of ramelteon, M-II, is pharmacologically active and has approximately one tenth and one fifth the binding affinity of the parent molecule for the human MT1 and MT2 receptors, respectively. However, M-II circulates at higher concentrations t

Approved indications

• Initial insomnia

Common side effects

• Somnolence
• Fatigue
• Dizziness
• Nausea
• Insomnia exacerbated

Key clinical trials

• Melatonin Agonist for Shift-time Workers. (PHASE4)
• Comparative Pharmacokinetic Study of Ramelteon Modified-Release Tablets and Ramelteon Tablets in Healthy Subjects (PHASE1)
• The Study of Combination Use of Melatonin Receptor Agonist for Dose Reduction or Interruptions of Benzodiazepine (BZD) and Non-BZD Hypnotics on Chronic Insomnia (PHASE4)
• Delirium Reduction With Ramelteon (PHASE4)
• A Study of Ramelteon in Chinese Patients With Chronic Insomnia (PHASE3)
• The Effect of Ramelteon on Delirium and Sleep in Patients Admitted to the ICU (PHASE4)
• Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism (NA)
• Treatment of Insomnia in Elderly Sleep Apnea Patients With Ramelteon (TAK 375) (PHASE3)

Primary sources

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