Ramelteon

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Cat Number

API196597269

CAS Number

196597-26-9

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Product Detail Description Scientific Support Customer Q&A

CAS Number

196597-26-9

EINECS

688-929-3

Storage

Store at room temperature

Synonyms

Rozerem; TAK-375; (S)-N-(2-(1,6,7,8-tetrahydro-2H-indeno-(5,4)furan-8-yl)ethyl)propionamide; 901AS54I69

Molecular Formula

C16H21NO2

Molecular Weight

259.3

Smiles

CCC(=O)NCC[C@@H]1CCC2=C1C3=C(C=C2)OCC3

Appearance

White to almost white powder to crystal

Melting Point

113-115°C

Boiling Point

455.3±24.0°C at 760 mmHg (Predicted)

Relative Density

1.119±0.06 (Predicted)

General Description

Ramelteon is a tricyclic synthetic analogue of melatonin, with a 1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan core. Unlike melatonin, ramelteon contains a cyclopropane ring and an ethyl side chain that increase affinity and selectivity for melatonin MT1 and MT2 receptors. The molecule has no significant affinity for MT3 receptors or other neurotransmitter receptors.

Mechanism of Action

Ramelteon acts as a selective, high‑affinity agonist at MT1 and MT2 melatonin receptors, with approximately five‑fold higher affinity than endogenous melatonin. Activation of MT1 receptors in the suprachiasmatic nucleus (SCN) inhibits the firing of SCN neurons, while MT2 activation phase‑shifts the circadian clock. The net effect is promotion of sleep onset without direct hypnotic effects on GABA receptors.

Application

Ramelteon is indicated for the treatment of insomnia characterized by difficulty with sleep onset (not sleep maintenance). It is the only prescription melatonin receptor agonist approved for chronic insomnia. Unlike benzodiazepines, it does not cause rebound insomnia or withdrawal symptoms, but its efficacy is modest, with a mean reduction in sleep latency of about 10‑15 minutes.

In a quadruple‑masked randomized placebo‑controlled trial (80 older patients undergoing hip or knee replacement), ramelteon 8 mg for 3 nights (starting preoperatively) did not reduce postoperative delirium incidence (9% vs. 5% for placebo, adjusted OR 1.28, 95% CI 0.21‑7.93, p=0.79). Adverse events were similar between groups. Ramelteon was not efficacious for preventing delirium in this setting.

Fig. 1 Consolidated Standard of Reporting Diagram for RECOVER study. (Oh ES, et al., 2021)

References

Oh ES, et al. Effects of Ramelteon on the Prevention of Postoperative Delirium in Older Patients Undergoing Orthopedic Surgery: The RECOVER Randomized Controlled Trial. Am J Geriatr Psychiatry. 2021;29(1):90-100.

Does Ramelteon require protection from light and heat during storage?

Yes, it is sensitive to both. Light causes photodegradation; heat accelerates oxidation of the indene ring. Store in light-resistant, airtight containers at controlled room temperature (15-25°C).

Is Ramelteon hygroscopic, and how is this managed?

It is slightly hygroscopic. Under high humidity (>70% RH), it may absorb moisture and clump. Storage in tightly sealed containers with desiccant is recommended.

Is Ramelteon stable in tablet formulations with standard excipients?

Yes, when formulated with moisture-protective packaging.

How is the impurity ramelteon 2-oxo (oxidation product) monitored?

This degradation product is specifically quantified using a stability-indicating HPLC method, ensuring it remains within ICH limits.