A Therapeutic Role For Melatonin Antagonism in Experimental Models of Parkinson’s Disease

Insomnia, sleep fragmentation and excessive daytime sleepiness are common in Parkinson's disease (PD) and may contribute to the reduction of cognition and alertness in those patients. Melatonin has been shown to improve sleep in several conditions. In experimental models of PD, melatonin can ameliorate motor symptoms. To evaluate the effect of melatonin on sleep and motor dysfuntion in PD, we studied 18 patients (Hoehn & Yahr I to III) from a PD clinic. Prior to treatment, motor dysfunction was assessed by UPDRS II, III and IV. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence by the Epworth Sleepiness Scale (ESS). Full polysomnography (PSG) was performed in all subjects. Patients were then randomized to receive melatonin (3mg) or placebo one hour before bedtime for four weeks. All measures were repeated at the end of treatment. On initial assessment, 14 patients (70%) showed poor quality sleep (PSQI > 6) and eight (40%) excessive daytime sleepiness (ESS > 10). Increased sleep latency (50%), REM sleep without atonia (66%), and reduced sleep efficiency (72%) were found on PSG. Eight patients had an apnea/ hipopnea index greater than 15 but no severe oxygen desaturation was observed. Sleep fragmentation tended to be more severe in patients on lower doses of levodopa (p = 0.07). Although melatonin significantly improved subjective quality of sleep (p = 0.03) as evaluated by the PSQI index, PSG abnormalities were not changed. Motor dysfunction was not improved by the use of melatonin. Undetected differences in motor scores and PSG findings may have been due to a small sample size and a type II error.

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“…In contrast, intracerebral injection of melatonin has been described to worsen striatal lesions in rats [12].…”

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confidence: 94%

Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease

et al. 2007

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“…Melatonin is a potent drug and will undoubtedly have side effects. Animal data suggest that melatonin may accelerate the course of Parkinson's disease (55). Melatonin is involved in sexual maturation, and hypermelatonism is being discussed as a cause of infertility (56).…”

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confidence: 99%

Melatonin in Patients with Reduced REM Sleep Duration: Two Randomized Controlled Trials

Kunz

Mahlberg

Müller

et al. 2004

The Journal of Clinical Endocrinology & Metabolism

117

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Recent data suggest that melatonin may influence human physiology, including the sleep-wake cycle, in a time-dependent manner via the body's internal clock. Rapid-eye-movement (REM) sleep expression is strongly circadian modulated, and the impact of REM sleep on primary brain functions, metabolic processes, and immune system function has become increasingly clear over the past decade. In our study, we evaluated the effects of exogenous melatonin on disturbed REM sleep in humans. Fourteen consecutive outpatients (five women, nine men; mean age, 50 yr) with unselected neuropsychiatric sleep disorders and reduced REM sleep duration (25% or more below age norm according to diagnostic polysomnography) were included in two consecutive, randomized, double-blind, placebo-controlled, parallel design clinical trials. Patients received 3 mg melatonin daily, administered between 2200 and 2300 h for 4 wk. The results of the study show that melatonin was significantly more effective than placebo: patients on melatonin experienced significant increases in

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“…For instance, reduction of melatonin by pinealectomy, or by exposure of rats to bright light to inhibit melatonin synthesis, has been found to enhance recovery from parkinsonism, i.e., spontaneous remission of symptoms following 6-OHDA or MPTP have been observed, whereas melatonin administration aggravated them (Willis and Armstrong 1999 ;Tapias et al 2010 ), using a rotenone model of PD in rats, found that melatonin administration led to striatal catecholamine depletion, striatal terminal loss, and nigral DA cell loss and thus was not neuroprotective. Indeed, the use of melatonin as an adjunct therapy to either halt progressive degeneration or for providing symptomatic relief in PD patients has been questioned (Willis and Robertson 2004 ).…”

Section: Basic Aspects Of Melatonin Activity In Animal Models Of Pdmentioning

confidence: 99%

Therapeutical Implications of Melatonin in Alzheimer’s and Parkinson’s Diseases

Cardinali

Vigo

Olivar

et al. 2015

Molecular and Integrative Toxicology

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Neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) are major health problems, and a growing recognition exists that efforts to prevent them must be undertaken by both governmental and nongovernmental organizations. In this context, the pineal product melatonin has a promising signifi cance because of its chronobiotic/cytoprotective properties. One of the features of advancing age is the gradual decrease in endogenous melatonin synthesis. A limited number of therapeutic trials have indicated that melatonin has a potential therapeutic value as a neuroprotective drug in the treatment of AD, minimal cognitive impairment (which may evolve to AD), and PD. Both in vitro and in vivo, melatonin prevented the neurodegeneration seen in experimental models of AD and PD. For these effects to occur, doses of melatonin about two orders of magnitude higher than those required to affect sleep and circadian rhythmicity are needed. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50-100 mg/day are needed to assess its therapeutic validity in neurodegenerative disorders.

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A Therapeutic Role For Melatonin Antagonism in Experimental Models of Parkinson’s Disease

Cited by 79 publications

References 65 publications

Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease

Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease

Melatonin in Patients with Reduced REM Sleep Duration: Two Randomized Controlled Trials

Therapeutical Implications of Melatonin in Alzheimer’s and Parkinson’s Diseases

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