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991.
Ramelteon is a novel hypnotic compound that is FDA-approved for the treatment of sleep-onset difficulty. It is a melatonin 1/2 receptor agonist with rapid absorption, extensive first-pass metabolism and an elimination half-life of just over 1h. Clinical efficacy data indicate moderate efficacy in reduction of sleep latency in adults of all ages with chronic insomnia, with estimated effect sizes roughly comparable to other standard hypnotic agents. Objective studies show minimal increases in total sleep time and no significant impact on wake after sleep-onset or sleep-stage distribution. Subjective reports demonstrate comparable, if slightly smaller, improvements. The recommended dosage is 8mg but studies suggest a flat response across dosage ranges from 4 to 32mg. Safety data indicate no evidence of clinically significant next-day performance effects and a reasonably low side effect profile. Animal studies, and a single human study suggest low abuse potential. Single-blind run-out from clinical trials have demonstrated no evidence of rebound insomnia. 相似文献
992.
Anderson KN Jamieson S Graham AJ Shneerson JM 《Clinical neurology and neurosurgery》2008,110(5):492-495
We report a case of a 68-year-old man with probable Alzheimer's disease who developed rapid eye movement (REM) sleep behaviour disorder. This was confirmed with polysomnography but the patient also had some sleep apnea, which prevented the use of clonazepam for treatment. Melatonin was successfully used as an alternative treatment. 相似文献
993.
目的 观察急性坏死性胰腺炎(ANP)大鼠肠道超微结构及其通透性的变化,探讨褪黑素(MT)对肠道屏障功能(IBF)的影响.方法 将72只SD大鼠随机分成ANP组、MT组、假手术组(SO组),各24只.ANP组和MT组大鼠采用胰胆管末端穿刺逆行注入5%牛磺胆酸钠制备ANP模型.MT组于制模前腹腔注射MT溶液.术后4、12、24、48 h处死动物,用ELISA法测血清肠脂肪酸结合蛋白(IFABP),光镜下观察末端回肠病理改变,电镜下观察回肠组织超微结构变化,TUNEL法观察肠上皮细胞凋亡情况.结果 SO组大鼠胰腺及回肠黏膜未见明显病理改变,回肠组织超微结构无明显变化,TUNEL法检查未见明显细胞凋亡;ANP组大鼠光镜下可见回肠柱状上皮细胞坏死、绒毛脱落,回肠超微结构异常最明显,上皮细胞微绒毛排列紊乱且短矮,TUNEL法提示回肠上皮凋亡细胞较多,以绒毛顶端为主;MT组大鼠病理改变、超微结构异常均较ANP组减轻,上皮凋亡细胞较ANP组减少.ANP组大鼠各时点血清IFABP水平较SO组显著升高,差异有统计学意义(P均<0.05);而MT组大鼠各时点血清IFABP水平较ANP组显著下降,差异亦有统计学意义(P均<0.05).结论 ANP可导致IBF障碍,肠上皮细胞有不同程度的坏死和凋亡.提示ANP发病早期肠道上皮细胞凋亡和增生之间失去平衡是IBF障碍的病理机制之一.予以MT干预,可以改善ANP发病后的肠道病理改变和肠道超微结构异常,其作用途径可能是通过抗氧化作用及抑制炎症反应,有待进一步的研究证实. 相似文献
994.
目的 探讨不同浓度褪黑激素对新生大鼠海马神经元电压门控性瞬时外向钾电流(I_A)的影响.方法 原代培养新生Wistar大鼠(出生时间<12 h)海马锥体神经元7~12 d.配制褪黑激素溶液,终浓度依次为1 nmol/L、10 nmol/L、100 nmol/L、1 μmol/L、10 μmol/L、100 μmol/L和1 mmol/L,选择胞体清晰、光晕良好、轴突明显的锥体神经元采用膜片钳全细胞记录模式记录I_A的基本电生理特点,记录不同浓度褪黑激素作用下I_A的动力学.结果 与褪黑激素作用前比较,1、10 nmol/L褪黑激素作用后海马锥体神经元I_A幅度升高(P<0.05),其余浓度褪黑激素作用前后海马锥体神经元I_A幅度比较差异无统计学意义(P>0.05);10 nmol/L褪黑激素作用后海马椎体神经元电压门控性瞬时外向钾通道激活曲线的半数激活膜电位及曲线斜率因子与褪黑激素作用前比较差异无统计学意义(P>0.05).结论 生理浓度褪黑激素可增加体外新生大鼠海马椎体神经元I_A. 相似文献
995.
Müslim Yurtçu Adnan Abasiyanik Mustafa Cihat Avunduk 《Journal of pediatric surgery》2009,44(9):1754-1758
Background/Purpose
This study aimed to compare dose schedules of the antioxidant treatment (melatonin and steroid) used as 1 dose and as once a day for 7 days in terms of salvage of the testes in the late period.Methods
Sixty prepubertal rats were divided into 6 groups each containing 10 rats: sham (S), torsion-detorsion (TD), 1-dose melatonin (M1), 1-dose steroid (ST1), 7-dose melatonin (M7), and 7-dose steroid (ST7) groups. The left testes were rotated 720° for 6 hours and detorsed for 6 hours thereafter. In the treatment groups, 17 mg/kg melatonin and 1 mg/kg steroid were injected 15 minutes before detorsion. Left orchiectomies were performed to determine testicular weights and Johnsen scores 3 months later.Results
Testicular weights and Johnsen scores in the M1, ST1, and TD groups were significantly lower compared with those in the S group, and atrophy developed in these groups, whereas they were higher in the M7 and ST7 groups compared with the TD group. Testicular atrophy did not develop in the M7 or ST7 groups.Conclusions
Our results suggested that antioxidant agents used once a day for 7 days prevent testicular atrophy and are effective in terms of salvage of the testes. 相似文献996.
Geert Mayer Sherry Wang-Weigand Barbara Roth-Schechter Reiner Lehmann Corinne Staner Markku Partinen 《Sleep》2009,32(3):351-360
Study Objectives:
Long-duration ( ≥ 6 months) polysomnographic studies of insomnia medications are lacking. This study evaluated the long-term efficacy of ramelteon, a selective MT1/MT2 melatonin-receptor agonist used for insomnia treatment.Design:
Six-month, randomized, double-blind, placebo-controlled study.Setting:
Forty-six investigative sites in the United States, Europe, Russia, and Australia.Participants:
Four hundred fifty-one adults (age ≥ 18 years) with chronic primary insomnia.Interventions:
Ramelteon, 8 mg, or placebo 30 minutes before bedtime nightly for 6 months.Measurements:
Sleep was evaluated by polysomnography and morning questionnaires on the first 2 nights of Week 1; the last 2 nights of Months 1, 3, 5, and 6; and Nights 1 and 2 of the placebo run-out. Next-morning residual effects as well as adverse effects and vital signs were recorded at each visit. Rebound insomnia and withdrawal effects were evaluated during placebo run-out.Results:
Over the 6 months of treatment, ramelteon consistently reduced latency to persistent sleep compared with baseline and with placebo; significant decreases were observed at Week 1 and Months 1, 3, 5, and 6 (P < 0.05). Ramelteon significantly reduced subjective sleep latency relative to placebo at Week 1, Month 1, and Month 5 (P < 0.05), with reductions nearing statistical significance at Months 3 and 6 (P ≤ 0.08). No significant next-morning residual effects were detected during ramelteon treatment. No withdrawal symptoms or rebound insomnia were detected after ramelteon discontinuation. Most adverse events were mild or moderate in severity.Conclusions:
In adults with chronic insomnia, long-term ramelteon treatment consistently reduced sleep onset, with no next-morning residual effects or rebound insomnia or withdrawal symptoms upon discontinuation.Citation:
Mayer G; Wang-Weigand S; Roth-Schechter B; Lehmann R; Staner C; Partinen M. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. SLEEP 2009;32(3):351–360. 相似文献997.
Secretion of melatonin by the mammalian pineal gland is primarily regulated by the release of norepinephrine (NE) from sympathetic nerve terminals that originate from the superior cervical ganglia. Peptidergic nerves that originate in the perikarya located in the sensory trigeminal ganglia also innervate the pineal gland. Some of these peptidergic nerve fibers contain substance P. Previously, we have characterized neurokinin 1 type substance P receptors in the pineal gland. However, the function of this receptor in the pineal gland remains unclear. Here, we examined the modulatory effect of substance P on rat pineal NE transmission. We show that at the presynaptic level, substance P stimulates the KCl-induced [3H]NE release from the pineal nerve ending. However, we found that substance P did not affect the basal levels of either arylalkylamine-N-acetyltransferase (AANAT) activity or melatonin secretion in rat pineal organ cultures. However, in the presence of NE, substance P inhibited the NE-induced increase in AANAT activity and melatonin secretion. This is the first time that a function for substance P in the mammalian pineal gland has been demonstrated. 相似文献
998.
Several novel melatonin receptor agonists, in addition to various formulations of melatonin itself, are either available or in development for the treatment of insomnia. Melatonin is thought to exert its effects principally through two high affinity, G-protein coupled receptors, MT1 and MT2, though it is not known which subtype is responsible for the sleep-promoting action. The present study used radiotelemetry to record EEG and EMG in un-restrained freely moving rats to monitor the sleep-wake behaviour and examined the acute sleep-promoting activity of an MT2 receptor subtype selective melatonin analog, IIK7. IIK7 is a full agonist at the MT2 receptor subtype but a partial agonist at the MT1 receptor and has ∼90-fold higher affinity for MT2 than MT1. Like melatonin, IIK7 (10 mg/kg i.p.) significantly reduced NREM sleep onset latency and transiently increased the time spent in NREM sleep, but did not alter REM sleep latency or the amount of REM sleep. An analysis of the EEG power spectrum showed no change in delta (1–4 Hz) or theta activity (5–8 Hz) following IIK7 administration. Core body temperature was slightly decreased (∼0.3 °C) by IIK7 compared to vehicle-treated rats. The acute and transient changes in the sleep-wake cycle mimic the changes seen with melatonin and suggest that its sleep-promoting activity is mediated by activation of the MT2 receptor subtype. 相似文献
999.
XIU-JING CAO MING WANG WEI-HENG CHEN DA-MIAO ZHU JIA-QI SHE DI-YUN RUAN 《Biomedical and environmental sciences : BES》2009,22(1):70-75
Objective To explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months. Methods Experiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo. Results Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. Conclusion Melatonin is not suitable for normal and lead-exposed children. 相似文献
1000.
Reyes-Toso CF Obaya-Naredo D Ricci CR Planells FM Pinto JE Linares LM Cardinali DP 《Experimental gerontology》2007,42(4):337-342
In old animals a marked reduction in endothelium-dependent relaxation occurs. Since there is evidence that the endothelial dysfunction associated with aging may be partly related to the local formation of reactive oxygen species, the purpose of this study was to examine the effect of the natural antioxidant melatonin (10(-5)mol/l) on in vitro contractility of aged aortic rings under conditions of increased oxidative stress (40 m mol/l glucose concentration in medium). Experiments were carried out in 18-20 months old, Wistar male rats, using adult (6-7 months old) animals as controls. A higher plasma lipid peroxidation was found in aged rats as compared to the younger ones. In a first experiment, dose-response curves for acetylcholine-induced relaxation of aortic rings were conducted. Analyzed as a main factor in a factorial ANOVA, age decreased and melatonin augmented the relaxing response to acetylcholine. melatonin's restoring effect on aortic ring relaxation was found in aged aortic rings only and was more pronounced in the presence of a high glucose medium. In a second experiment, the effect of melatonin on the contractility response to phenylephrine of intact or endothelium-denuded aortic rings obtained from aged or control rats was examined in normal or high glucose medium. A main factor analysis in the factorial ANOVA indicated that age and operation augmented, and melatonin decreased, aortic ring contractility response to phenylephrine. Melatonin's restoring effect on aortic contractility was seen in aged aortic rings. The effect of age or a high glucose medium on phenylephrine-induced contractility was more pronounced in the absence of an intact endothelium. Aging did not affect the relaxant response of intact or endothelium-denuded rings to sodium nitroprusside. The results support the improvement by melatonin of vascular response in aging rats, presumably via its antioxidant activity. 相似文献