Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TAK-375 (Ramelteon), a melatonin ML1/MT1 receptor agonist for the potential treatment of primary insomnia, is being developed by Takeda. Takeda submitted an NDA to the FDA for TAK-375 in September 2004.
 ...
PMID:TAK-375 Takeda. 1567 11

Ramelteon (TAK-375) is a novel melatonin receptor agonist currently under investigation for the treatment of insomnia. This study describes the neurochemical and receptor binding characteristics of ramelteon in vitro. Ramelteon showed very high affinity for human MT1 (Mel1a) and MT2 (Mel1b) receptors (expressed in Chinese hamster ovary [CHO] cells), and chick forebrain melatonin receptors (consisting of Mel1a and Mel1c receptors) with Ki values of 14.0, 112, and 23.1 pM, respectively, making the affinities of ramelteon for these receptors 3-16 times higher than those of melatonin. The affinity of ramelteon for hamster brain MT3 binding sites was extremely weak (Ki: 2.65 microM) compared to melatonin's affinity for the MT3 binding site (Ki: 24.1 nM). In addition, ramelteon showed no measurable affinity for a large number of ligand binding sites (including benzodiazepine receptors, dopamine receptors, opiate receptors, ion channels, and transporters) and no effect on the activity of various enzymes. Ramelteon inhibited forskolin-stimulated cAMP production in the CHO cells that express the human MT1 or MT2 receptors. Taken together, these results indicate that ramelteon is a potent and highly selective agonist of MT1/MT2 melatonin receptors.
 ...
PMID:Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. 1569 69

Ramelteon [TAK 375] is a melatonin (MT1/MT2) receptor agonist that is being developed by Takeda as a treatment for sleep disorders. It is undergoing regulatory review in the US, phase III trials in Europe, and phase II trials in Japan for the treatment of insomnia. Phase II trials are also being conducted in the US for the treatment of circadian rhythm sleep disordersIn September 2004, Takeda submitted an NDA to the US FDA for ramelteon for the treatment of insomnia. In May 2003, data presented at the 156th Annual Meeting of the American Psychiatric Association report that ramelteon is highly selective for the MT1 receptor, and has greater affinity, selectivity and potency than melatonin.
 ...
PMID:Ramelteon: TAK 375. 1586 23

Ramelteon, approved in the US for the treatment of insomnia characterised by difficulty with sleep onset, is a highly selective agonist for the melatonin MT1/MT2 receptors, which are believed to mediate the circadian rhythm in mammals. Ramelteon has negligible affinity for the MT3 binding sites and other receptors in the brain, including the opiate, dopamine, benzodiazepine and serotonin receptors, which may explain the lack of significant adverse events and lack of abuse or dependence potential observed with ramelteon. In three clinical trials in patients with chronic insomnia, ramelteon 8mg was effective in reducing sleep latency, without being associated with any significant or clinically relevant residual effects. It also generally increased total sleep time and, where assessed, sleep efficiency. In a first-night-effect model of transient insomnia, ramelteon 8mg was significantly more effective than placebo at reducing sleep latency and increasing total sleep time. Ramelteon was generally well tolerated; the most commonly reported adverse events occurring in more ramelteon than placebo recipients were somnolence (5% vs 3%), fatigue (4% vs 2%) and dizziness (5% vs 3%). Adverse events were mostly mild or moderate in nature. Ramelteon has been shown to have no potential for abuse or dependence.
 ...
PMID:Ramelteon. 1633 46

Ramelteon is a selective MT(1)/MT(2) receptor agonist, indicated for insomnia treatment. Safety, tolerance, pharmacokinetics, and cognitive performance were evaluated following increasing ramelteon doses. Healthy adults (35-65 years) were randomly assigned to receive 1 of 5 oral ramelteon doses (4, 8, 16, 32, or 64 mg; n = 8 per group) or placebo (n = 20). C(max) and AUC(infinity) (mean [%CV]) increased with each dose: C(max) = 1.15 (109), 5.73 (97), 6.92 (77), 17.4 (76), and 25.9 (77) ng/mL, respectively, and AUC(infinity) = 1.71 (114), 6.95 (108), 9.88 (78), 22.5 (80), and 36.1 (71 n x h/mL), respectively. Mean T(max) values of 0.75 to 0.94 hours and mean elimination half-life of 0.83 to 1.90 hours remained relatively constant. Ramelteon was extensively metabolized. Besides ramelteon, 4 metabolites, M-I, M-II, M-III, and M-IV, were measured in serum. Metabolite M-II, which has shown weak ramelteon-like activity in vitro, was the major metabolite in serum. Digit Symbol Substitution Test and visual analog scale alertness scores were similar across all dose groups and did not differ from placebo. All adverse events were mild or moderate and resolved before study completion.
 ...
PMID:Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia. 1643 65

To date the mainstay of the pharmacological treatment of insomnia has involved the modulation of the gabaminergic system via benzodiazepines or the Z-drugs, zolpidem, zopiclone or zaleplon. A new approach has explored the melatoninergic system, namely activation of MT1 and MT2 receptors in the suprachiasmatic nucleus of the hypothalamus. Ramelteon (TAK-375) is a novel sleep-promoting agent that acts as an agonist at these receptors; its preclinical pharmacology, mode of action, pharmacokinetics, drug interactions, clinical efficacy, and safety and tolerability are reviewed here.
 ...
PMID:Ramelteon: profile of a new sleep-promoting medication. 1670 22

This paper reviews the use of sleep-promoting medications in nursing home residents with reference to risks versus benefits. Up to two-thirds of elderly people living in institutions experience sleep disturbance. The aetiology of sleep disturbance includes poor sleep hygiene, medical and psychiatric disorders, sleep apnoea, periodic limb movements and restless leg syndrome. One key factor in the development of sleep disturbance in the nursing home is the environment, particularly with respect to high levels of night-time noise and light, low levels of daytime light, and care routines that do not promote sleep. Clinical assessment should include a comprehensive medical, psychiatric and sleep history including a review of prescribed medications. Nonpharmacological interventions for insomnia are underutilised in many clinical settings despite evidence that they are often highly effective. International studies suggest that 50-80% of nursing home residents have at least one prescription for psychotropic medication. Utilisation rates vary dramatically from country to country and from institution to institution. The most commonly prescribed medications for sleep are benzodiazepines and nonbenzodiazepine hypnotics (Z-drugs). The vast majority of studies of these medications are short-term, i.e. < or =2 weeks, although some longer extension trials have recently been carried out. Clinicians are advised to avoid long-acting benzodiazepines and to use hypnotics for as brief a period as possible, in most cases not exceeding 2-3 weeks of treatment. Patients receiving benzodiazepines are at increased risk of daytime sedation, falls, and cognitive and psychomotor impairment. Zaleplon, zolpidem, zopiclone and eszopiclone may have some advantages over the benzodiazepines, particularly with respect to the development of tolerance and dependence. Ramelteon, a novel agent with high selectivity for melatonin receptors, has recently been approved in the US. Use of the antidepressant trazodone for sleep in nondepressed patients is somewhat controversial. Atypical antipsychotics should not be used to treat insomnia unless there is also evidence of severe behavioural symptoms or psychosis.
 ...
PMID:Use of sleep-promoting medications in nursing home residents : risks versus benefits. 1673 87

Ramelteon, a potent agonist for the melatonin MT1 and MT2 brain receptors, has recently been granted approval by the US FDA for the treatment of insomnia associated with sleep onset. The drug has not exhibited potential for abuse or dependency in laboratory tests, nor does it interact with neurotransmitter receptors most associated with these phenomena, hence it has the great advantage of being a nonscheduled drug. Few data have been published in peer-reviewed journals describing its efficacy and side effects in patients with insomnia; however, side effects noted to date appear minor. No comparison study has been performed to determine whether the recommended dose of ramelteon 8 mg has any advantage over physiologic doses of melatonin (0.3 mg), particularly for long-term use.
 ...
PMID:Ramelteon: a novel treatment for the treatment of insomnia. 1683 Nov 11

Insomnia is one of the most common complaints faced in clinical practice. The limited pharmacological options available make the treatment of this complaint a challenge. All of the available benzodiazepines and non-benzodiazepine hypnotics have the potential to induce addiction, cause withdrawal symptoms, or trigger rebound insomnia. Further, the evidence supporting the utility of commonly prescribed options such as antidepressants and antipsychotics is limited. Melatonin is a hormone that has been associated with soporific effects. Based on this premise, a melatonin receptor agonist was created. Ramelteon was approved by the Food and Drug Administration in 2005 and is the only medication indicated for the long-term treatment of insomnia. A critical review with a clinical perspective of randomized, placebo-controlled clinical trials was conducted to determine the efficacy of melatonin and ramelteon for the treatment of insomnia. Based on this review, it appears that more placebo-controlled trials are indicated before valid judgments concerning the efficacy of both melatonin and ramelteon can be made. In the meantime, there is some support for the use of melatonin for the treatment of insomnia, and findings concerning ramelteon also appear promising. Nevertheless, clinicians who prescribe melatonin or ramelteon should be cautious and carefully monitor both potential benefits and adverse effects, since data on melatonin are based on studies with multiple limitations and only three controlled trials have been done with ramelteon.
 ...
PMID:Searching for new options for treating insomnia: are melatonin and ramelteon beneficial? 1688 48

Ramelteon is a selective MT(1)/MT(2)-receptor agonist indicated for insomnia treatment. Because it has no depressant effects on the nervous system, it is not expected to affect the control of breathing. The potential effects of ramelteon on apneic and hypopneic events and arterial oxygen saturation (SaO(2)) in individuals with obstructive sleep apnea were assessed. In this double-blind, randomized, crossover study, 26 adults with mild to moderate obstructive sleep apnea received ramelteon 16 mg and placebo for one night each, with a 5- to 12-day washout period between treatments. Treatments were administered 30 min before habitual bedtime. Respiratory effort was monitored using respiratory inductance plethysmography, SaO(2) was measured by pulse oximetry, and sleep onset and duration were measured by polysomnography and post-sleep questionnaire. Post-sleep questionnaire also measured next-day residual effects. The primary measure was apnea-hypopnea index. Apnea-hypopnea index was similar in ramelteon and placebo groups (11.4 vs 11.1, respectively; CI = -2.1, 2.6, P = 0.812). Ramelteon had no effect on the number of central, obstructive, or mixed apnea episodes. No significant differences were observed in SaO(2) for the entire night between ramelteon and placebo (95.1 vs 94.7%; P = 0.070). Ramelteon did not meaningfully affect sleep when evaluated by polysomnography and post-sleep questionnaire. Compared with placebo, ramelteon had no significant effect on next-day residual effects. Adverse events were reported by three subjects in the ramelteon group: headache (n = 2) and urinary tract infection (n = 1). No adverse events were reported with placebo. Ramelteon was well-tolerated and, as expected, did not worsen sleep apnea when administered to subjects with mild to moderate obstructive sleep apnea.
 ...
PMID:Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea. 1729 32


1 2 3 4 5 Next >>