Ramelteon: A Novel Approach in the Treatment of Insomnia

Reynoldson, Jill N.; Elliott, Ellie; Nelson, Leigh Anne

doi:10.1345/aph.1k676

Cited by 25 publications

(8 citation statements)

References 16 publications

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“…Melatonin levels appear to decline with aging, and are lower in elderly insomniacs than in age‐matched controls. Ramelteon is the first melatonin receptor agonist approved by the FDA for the treatment of insomnia 102 . Ramelteon has high affinity for the MT 1 and MT 2 receptors located in the suprachiasmatic nucleus (SCN), which is responsible for generation and modulation of the circadian rhythm.…”

Section: Methodsmentioning

confidence: 99%

Late‐life insomnia: A review

Fetveit

2009

Geriatrics Gerontology Int

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Aging is associated with substantial changes in sleep patterns, which are almost always negative in nature. Typical findings in the elderly include a reduction in the deeper stages of sleep and a profound increase in the fragmentation of nighttime sleep by periods of wakefulness. The prevalence of specific sleep disorders increases with age, such as a phase advance in the normal circadian sleep cycle, restless legs syndrome, and obstructive sleep apnea, which is increasingly seen among older individuals and is significantly associated with cardio‐ and cerebrovascular disease as well as cognitive impairment. Elderly patients with sleep disturbances are often considered difficult to treat; yet, they are among the groups with the greatest need of treatment. Management of sleep disturbances begins with recognition and adequate assessment. Hypnotic drugs have clearly been shown to improve subjective and objective sleep measures in short‐term situations, but their role in chronic insomnia still remains to be further defined by research evidence. Non‐pharmacological treatments, particularly stimulus control and sleep restriction, are effective for conditioned aspects of insomnia and are associated with a stable, long‐term improvement in sleep. This review delineates the common causes of disordered sleep in older individuals, and effective diagnostic approaches and treatments for these conditions.

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Section: Methodsmentioning

confidence: 99%

Late‐life insomnia: A review

Fetveit

2009

Geriatrics Gerontology Int

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“…The orexin system mainly promotes arousal; orexin antagonists have the potential to selectively promote sleep [27][28][29][30] and have fewer side effects [22]. Melatonin agonist drugs (eg, melatonin [31][32][33][34][35], ramelteon [36][37][38][39][40]) and antihistamine drugs (eg, diphenhydramine) [27][28][29][30] have also been studied extensively in recent years [41].…”

Section: Discussionmentioning

confidence: 99%

Publication analysis on insomnia: how much has been done in the past two decades?

Dong²,

Mita

et al. 2015

Sleep Medicine

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“…CYP1A2 is the primary isoenzyme responsible for ramelteon's metabolism to its major active metabolite, M‐II (Obach & Ryder, ). The concentration of M‐II in plasma is much higher, resulting in a 20‐ to 100‐fold greater overall mean systemic exposure than that of ramelteon (Reynoldson, Elliott, & Nelson, ). Despite the lower affinity, M‐II exhibited a selectivity for MT 1 and MT 2 receptors and the considerably higher blood levels showed that this metabolite might substantially contribute to ramelteon's overall activity (Greenblatt, Harmatz, & Karim, ; Pandiperumal et al, ).…”

Section: Introductionmentioning

confidence: 99%

LC–MS/MS method for simultaneous determination of ramelteon and its metabolite M‐II in human plasma: Application to a clinical pharmacokinetic study in healthy Chinese volunteers

Zhu

et al. 2019

Biomedical Chromatography

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A sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of ramelteon and its active metabolite M‐II in human plasma. After extraction from 200 μL of plasma by protein precipitation, the analytes and internal standard (IS) diazepam were separated on a Hedera ODS‐2 (5 μm, 150 × 2.1 mm) column with a mobile phase consisted of methanol–0.1% formic acid in 10 mm ammonium acetate solution (85:15, v/v) delivered at a flow rate of 0.5 mL/min. Mass spectrometric detection was operated in positive multiple reaction monitoring mode. The calibration curves were linear over the concentration range of 0.0500–30.0 ng/mL for ramelteon and 1.00–250 ng/mL for M‐II, respectively. This method was successfully applied to a clinical pharmacokinetic study in healthy Chinese volunteers after a single oral administration of ramelteon. The maximum plasma concentration (Cmax), the time to the Cmax and the elimination half‐life for ramelteon were 4.50 ± 4.64ng/mL, 0.8 ± 0.4h and 1.0 ± 0.9 h, respectively, and for M‐II were 136 ± 36 ng/mL, 1.1 ± 0.5 h, 2.1 ± 0.4 h, respectively.

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Ramelteon: A Novel Approach in the Treatment of Insomnia

Cited by 25 publications

References 16 publications

Late‐life insomnia: A review

Late‐life insomnia: A review

Publication analysis on insomnia: how much has been done in the past two decades?

LC–MS/MS method for simultaneous determination of ramelteon and its metabolite M‐II in human plasma: Application to a clinical pharmacokinetic study in healthy Chinese volunteers

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