Melatonin in Epilepsy: First Results of Replacement Therapy and First Clinical Results

Fauteck, Jan-Dirk; Schmidt, Helmut S.; Lerchl, Alexander; Kurlemann, Gerhard; Wittkowski, W.

doi:10.1159/000014577

Cited by 110 publications

(55 citation statements)

References 16 publications

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“…The anti-excitatory effects of melatonin are probably secondary to its antioxidant effect [5]. When it is administered in pharmacological doses in children, it leads to reduction in severity and frequency of epileptiform activity [6]. It shows an effect contrary to glutamate, which is an excitatory neurotransmitter, i.e.…”

Section: öZmentioning

confidence: 99%

A Review of Melatonin, Its Receptors and Drugs

et al. 2016

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After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activityregulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future. Keywords: Melatonin, receptors, agonists, pineal gland ÖzSaat genlerini anlamamıza olan katkısından dolayı bir Türk bilim adamı Nobel ödülünü aldıktan sonra, bu genlerle yakın ilişkili olan melatoninin önemi arttı. Melatonin, pineal bezden gece salınan bir hormondur, uyku/uyanıklık döngüsünde, pubertal gelişimde ve mevsimsel adaptasyonda rol alır. Melatoninin antinosiseptif, antidepresan, anksiyolitik, antineofobik, locomotor aktiviteyi düzenleyici, nöroprotektif, antiinflamatuvar, ağrı dü-zenleyici, kan basıncını düşürücü, retinal, vasküler, tümör baskılayıcı ve antioksidan etkileri vardır. Hafıza, over fizyolojisi ve osteoblast diferansiasyonuyla ilişkilidir. Melatonin seviyelerinde artış veya azalışla seyreden patolojiler derlemede özetlenmiştir. Melatonin 4 mekanizmayla etkir: 1) Plazma membranında melatonin reseptörlerine bağlanma, 2) Kalmodulin gibi hücre içi reseptörlere bağlanma, 3) Yetim nükleer reseptörlere bağlanma, 4) Antioksidan etkiler. Melatoninle ilişkili reseptörler şunlardır: 1) Melatonin reseptör tip1a: MT1 (hücre zarında), 2) Melatonin reseptör tip1b: MT2 (hücre zarında), 3) Melatonin reseptör tip1c (balık, amfibiler ve kuşlarda bulunur), 4) Kuinon redüktaz-2 enzimi (MT3 reseptörü, bir detoksifika...

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Section: öZmentioning

confidence: 99%

A Review of Melatonin, Its Receptors and Drugs

et al. 2016

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“…Seizure is one of the primary causes of oxidative stress that induced neuronal cell death. Recently, melatonin is discussed in relation to epileptic seizure [100][101][102]. Melatonin has been known for antioxidant as a free radical scavenger.…”

Section: Neuroprotective Effect Of Melatonin On Seizures In Autistic Fxsmentioning

confidence: 99%

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

Won

Jin

Lee

et al. 2017

Preprint

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Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

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“…Furthermore, studies have reported that the primary beneficial effect of melatonin on seizure activity is due to its ability to synchronize disturbed circadian rhythms in epileptic patients (Fauteck et al, 1999;Peled et al, 2001). Comorbidity of a sleep disorder with epilepsy creates difficulties in choosing an anti-epileptic drug (AED).…”

Section: Melatonin and Epilepsymentioning

confidence: 99%

“…In line with this, melatonin and melatonin receptor agonists may be suitable for use as add-on treatments with routine AEDs. Indeed, melatonin alleviates sleep disturbances of different etiologies in epileptic children and adults (Coppola et al, 2004;Fauteck et al, 1999;Peled et al, 2001). …”

Section: Melatonin and Epilepsymentioning

confidence: 99%

The role of the melatoninergic system in epilepsy and comorbid psychiatric disorders

Tchekalarova

Moyanova

Fusco

et al. 2015

Brain Research Bulletin

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Abstract\ud \ud There is emerging evidence of the beneficial role of the melatonin system in a wide range of psychiatric and neurologic disorders, including anxiety, depression, and epilepsy. Although melatoninergic drugs have chronobiotic and antioxidant properties that positively influence circadian rhythm desynchronization and neuroprotection in neurodegenerative disorders, studies examining the use of melatonin for epilepsy's comorbid psychiatric and neurological symptomatology are still limited. Preclinical and clinical findings on the beneficial effects of the melatonin system on anxiety, depression, and epilepsy suggest that melatoninergic compounds might be effective in treating comorbid behavioral complications in epilepsy beyond regulation of a disturbed sleep-wake cycle

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Melatonin in Epilepsy: First Results of Replacement Therapy and First Clinical Results

Cited by 110 publications

References 16 publications

A Review of Melatonin, Its Receptors and Drugs

A Review of Melatonin, Its Receptors and Drugs

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

The role of the melatoninergic system in epilepsy and comorbid psychiatric disorders

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