Ramelteon (Rozerem)

Indicated for the treatment of insomnia characterized by difficulty in sleep onset.



Approved for the treatment of insomnia characterized by difficulty with sleep onset.



A sleep agent medication that selectively binds to the MT1 and MT2 receptors in the suprachiasmatic nucleus, 



Trade name Rozerem



Routes of administration-By mouth



Bioavailability 1.8%



Protein binding 82%



Metabolism Hepatic (CYP1A2-mediated)



Elimination half-life 1–2.6 hours



Excretion Renal (84%) and fecal (4%)



It speeds the onset of sleep and alter the total amount of sleep a person gets.



Approved for long-term use.



Does not have appreciable binding to GABAA receptors, which are associated with anxiolytic, myorelaxant, and amnesic effects.



Beneficial in preventing delirium in medically ill individuals when compared to placebo.



Not associated with potential for abuse, or withdrawal and rebound insomnia that is typical with GABA modulators.



Six percent of patients discontinued the drug due to an adverse events.



Adverse events: somnolence, dizziness, nausea, fatigue, headache, and insomnia. 



Rare cases of anaphylactic reactions, abnormal thinking, and suicide in patients with pre-existing depression have been reported.



When coadministered with ramelteon, fluvoxamine a strong CYP1A2 inhibitor increased AUC approximately 190-fold, and the Cmax increased approximately 70-fold, compared to ramelteon administered alone. 



Ramelteon and fluvoxamine should not be coadministered.



It has significant drug–drug interactions with: amiodarone, ciprofloxacin, fluvoxamine, ticlopidine.



It should be administered with caution in patients taking other CYP1A2 inhibitors, strong CYP3A4 inhibitors such as ketoconazole, and strong CYP2C9 inhibitors such as fluconazole.



It is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the MT3 receptor. 



Its  activity at the MT1 and MT2 receptors contribute to its sleep-promoting properties..



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, receptors that bind neuropeptides, cytokines, serotonin, dopamine, noradrenaline, acetylcholine, and opioids. 



The major metabolite of ramelteon, M-II, is active and has approximately one tenth and one fifth the binding affinity of the parent molecule for the human MT1.


and MT2 receptors, respectively.



The potency of M-II at MT1 and MT2 receptors is lower than the parent drug, M-II circulates at higher concentrations than the parent producing 20–100-fold greater mean systemic exposure when compared to ramelteon. 



MT1 and MT2 melatonin receptor selective agonist with minimal affinity for other sites implicated for abuse and impaired functions as benzodiazepine receptors, dopamine receptors, opiate receptors, ion channels and various receptor transporters.

MT1 and MT2 receptors located in the suprachiasmatic nucleus of the hypothalamus and help maintain circadian sleep-wake cycles.

Rare cases associated with anaphylaxis.

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