Antiepileptic activity of melatonin in guinea pigs with pentylenetetrazol-induced seizures

Solmaz, İlker; Gürkanlar, Doğa; Gökçil, Zeki; Goksoy, Cuneyt; Özkan, Mehmet; Erdoğan, Ersin

doi:10.1179/174313209x385545

Cited by 48 publications

(22 citation statements)

References 55 publications

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“…Similarly with previously reported results on the anticonvulsant effects of melatonin at doses ranging from 40 to 80 mg/kg in PTZinduced seizures in a variety of species (Bikjdaouene et al, 2003;Moezi et al, 2011;Solmaz et al, 2009;Yahyavi-Firouz-Abadi et al, 2007), the authors showed that agomelatine was active at doses of 25 and 50 mg/kg. Agomelatine was also effective against pilocarpineinduced SE at a dose of 75 mg/kg (Aguiar et al, 2012), while melatonin had an anticonvulsant effect only after repeated injections in this model of epilepsy (Costa-Lotufo et al, 2002;De Lima et al, 2011).…”

Section: Melatonin and Epilepsysupporting

confidence: 63%

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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Section: Melatonin and Epilepsysupporting

confidence: 63%

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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“…The anticonvulsant activity exerted by MT seen in animal models of epilepsy (Golombek et al, 1992, 1996; Cardinali et al, 2008; Solmaz et al, 2009) has been suggested to be executed via increasing the activity of GABAergic system (Golombek et al, 1996). A selective MT 1 /MT 2 R agonist mimicked the MT effects in rat rapid kindling model and in the spontaneously epileptic mice lacking voltage-gated Kv1.1 channels (Kcna1-null mice; Fenoglio-Simeone et al, 2009).…”

Section: Monoamines In Epilepsy: Preclinical and Clinical Evidencementioning

confidence: 99%

Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

et al. 2016

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A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders.

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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: 50%

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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Antiepileptic activity of melatonin in guinea pigs with pentylenetetrazol-induced seizures

Abstract: Although melatonin does not have a primary anticonvulsant effect at low doses (10 mg/kg), it lowers the mortality rates and attenuates seizure severity while increasing the latent period.

Cited by 48 publications

References 55 publications

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

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

Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

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

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