Anticonvulsant effects of the selective melatonin receptor agonist ramelteon

Fenoglio-Simeone, Kristina A.; Mazarati, Andréy; Sefidvash-Hockley, Sepideh; Shin, Don; Wilke, Julianne; Milligan, Heather L.; Sankar, Raman; Rho, Jong M.; Maganti, Rama

doi:10.1016/j.yebeh.2009.07.022

Cited by 49 publications

(44 citation statements)

References 23 publications

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“…Moreover, melatonin has been recommended for use in children with epilepsy since it has been shown to improve the quantity and quality of sleep, thus reducing the probability of sleep deprivation induced seizures in these patients [9,10]. Animal research has demonstrated that melatonin suppresses epileptic discharges [5,20].…”

Section: Introductionmentioning

confidence: 99%

Melatonin does not influence sleep deprivation electroencephalogram recordings in children

et al. 2011

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Section: Introductionmentioning

confidence: 99%

Melatonin does not influence sleep deprivation electroencephalogram recordings in children

et al. 2011

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“…see [71]). Such anticonvulsant action of melatonin could be attributed to both MT 1 and MT 2 receptors [25,[72][73][74][75][76] and similar anti-seizure effects were observed with the MT 1 / MT 2 agonist ramelteon [77]. These antiexcitatory actions are also related to the anxiolytic, antihyperalgesic and antinociceptive effects of melatonergic agents [78][79][80][81][82][83].…”

Section: Melatonin and Brain Gabaergic Mechanismsmentioning

confidence: 64%

Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse

Cardinali

Golombék

Rosenstein

et al. 2016

Pharmacological Research

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The abuse of benzodiazepine (BZP) and Z drugs has become, due to the tolerance and dependence they produce, a serious public health problem. Thirty years ago, we demonstrated in experimental animals the interaction of melatonin with central BZD receptors, and in 1997 we published the first series of elderly patients who reduced BZP consumption after melatonin treatment. Almost every single neuron in the hypothalamic suprachiasmatic nuclei (SCN), the central pacemaker of the circadian system, contains γ-aminobutyric acid (GABA) and many results in animals point out to a melatonin interaction with GABA-containing neurons. In addition, central-type BZD antagonism, that obliterates GABAA receptor function, blunted most behavioral effects of melatonin including sleep. Melatonin is involved in the regulation of human sleep. This is supported by the temporal relationship between the rise of plasma melatonin levels and sleep propensity as well as by the sleep-promoting effects of exogenously administered melatonin. Both meta-analyses and consensus agreements give support to the therapeutic use of melatonin in sleep disorders. This action is attributed to MT1 and MT2 melatoninergic receptors localized in the SCN, as well as in other brain areas. This review discusses available data on the efficacy of melatonin to curtail chronic BZD/Z drug use in insomnia patients. A major advantage is that melatonin has a very safe profile, it is usually remarkably well tolerated and, in some studies, it has been administered to patients at very large doses and for long periods of time, without any potentiality of abuse. Further studies on this application of melatonin are warranted.

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“…In this specific context, the facilitatory role of melatonin (1) on GABAergic transmission has been emphasized [146], but a contribution of additional effects, e.g., on NO formation may not be excluded. The anticonvulsant activity of melatonin (1) is mediated by MT 1 and/or MT 2 receptors, since corresponding effects have been observed with the synthetic MT 1 /MT 2 -selective melatonergic agonist ramelteon (12) [147].…”

Section: Effects Of Melatonin In the Central Nervous Systemmentioning

confidence: 98%

Melatonin and Synthetic Melatonergic Agonists: Actions and Metabolism in the Central Nervous System

Hardeland¹,

Pöeggeler²

2012

CNSAMC

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The CNS is both source and target of melatonin. This methoxyindole formed in the pineal gland is also produced in other CNS regions and additionally enters the brain by uptake from the circulation as well as via the pineal recess. The mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN), not only controls the pineal, but also receives a feedback information on darkness. Two G protein-coupled melatonin receptors, MT1 and MT2, are responsible for the transduction of many melatonergic actions. High receptor densities are especially found in the SCN, but their presence at lower expression levels in other areas is functionally important. Various metabolites and analogs are formed in the CNS, such as N-acetylserotonin, 5-methoxytryptamine, 5-methoxytryptophol, 5-methoxylated kynuramines, and even 6-sulfatoxymelatonin. The chronobiological effects of melatonin go beyond the resetting of a single circadian oscillator. They contribute to phase relationships between oscillatory subsets and are required for robust rhythm amplitudes. CNS effects of melatonin comprise sleep initiation, antiexcitatory, antiepileptic, antinociceptive, anxiolytic, proneurotrophic, antiinflammatory, antioxidant and other neuroprotective actions. The role as a sleep-promoting compound, which is limited by its short half-life in the circulation, has led to the development of controlled-release formulations and of various synthetic agonists, such as ramelteon, agomelatine, tasimelteon, TIK-301, UCM765 and UCM924. Their differences concerning receptor affinities, preferences for receptor subtypes, and pharmacokinetics are discussed, as well as additional antidepressive actions of agomelatine and TIK-301 based on properties as antagonists of the serotonergic 5-HT2C receptor. Indirect antidepressive effects by melatonergic drugs are largely explained by circadian readjustments.

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Anticonvulsant effects of the selective melatonin receptor agonist ramelteon

Cited by 49 publications

References 23 publications

Melatonin does not influence sleep deprivation electroencephalogram recordings in children

Melatonin does not influence sleep deprivation electroencephalogram recordings in children

Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse

Melatonin and Synthetic Melatonergic Agonists: Actions and Metabolism in the Central Nervous System

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