Anticonvulsant effects of agomelatine in mice

Aguiar, Carlos Clayton Torres; Almeida, Anália Barbosa; Araújo, Paulo Victor Pontes; Vasconcelos, Germana Silva; Chaves, Edna Maria Camelo; Vale, Otoni Cardoso do; Macêdo, Danielle Silveira; Sousa, Francisca Cléa Florenço de; Viana, Glauce Socorro de Barros; Vasconcelos, Silvânia Maria Mendes

doi:10.1016/j.yebeh.2012.04.134

Cited by 37 publications

(27 citation statements)

References 29 publications

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“…The effects of melatonin appear to be receptor-dependent, as co-administration of melatonin receptor antagonists have been shown to block the anticonvulsant effect of melatonin in several seizure models ((Moezi et al, 2011; Ray et al, 2004). Moreover, several melatonin receptor agonists have been shown to exert anticonvulsant effects in animal models (Aguiar et al, 2012; Fenoglio-Simeone et al, 2009). The degree to which specific receptors or signaling cascades contribute to the potentiation of phenobarbital’s anticonvulsant effect by melatonin in the present manuscript remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats

et al. 2013

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Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital, the most commonly utilized anticonvulsant in neonatal medicine. Postnatal day (P)7 rats were treated with phenobarbital (0–40 mg/kg) and/or melatonin (0–80 mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100 mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy.

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Section: Discussionmentioning

confidence: 99%

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats

et al. 2013

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“…It was recently approved as an antidepressant medication with comparable efficacy to classical antidepressant drugs (Sansone and Sansone, 2011). Agomelatine has anticonvulsant activity shown in PTZ- or pilocarpine-induced seizure models due to its combined action at MT1/2 and 5-HT 2C Rs (Aguiar et al, 2012). …”

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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“…Gupta and Sharma (2014) reported that levels of oxidative stress and mitochondrial enzyme complexes (I, II, and IV) in rat brain striatum were reduced in a rat model of Huntington disease induced by agomelatine treatment. Agomelatine is an agonist of melatonin receptors and vanillin (Aguiar et al, 2012(Aguiar et al, , 2013. Figure. ROS production can induce seizure activity through direct activation of glutamine synthetase, thereby permitting an abnormal buildup of excitatory neurotransmitter glutamate (Nazıroğlu, 2009).…”

Section: Melatonin and Trp Channelsmentioning

confidence: 99%

Role of melatonin on calcium signaling and mitochondrial oxidativestress in epilepsy: focus on TRP channels

Nazıroğlu¹

2015

Turk J Biol

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Calcium ion (Ca 2+ ) accumulation and excessive oxidative stress in the hippocampus and brain cortex have long been known as major contributors to the etiology of epilepsy. I have reviewed the role of Ca 2+ signaling through cation channels and mitochondriamediated oxidative stress on epilepsy in human and animals. A review of the relevant papers and results from recent studies were obtained from PubMed and the Science Citation Index. Current literature findings indicate that melatonin and agomelatine reduce activation of hippocampal transient receptor potential (TRP), glutamate receptors, and voltage-gated calcium channels that are critical for the development of abnormal Ca 2+ homeostasis and oxidative stress and associated mitochondrial dysfunction. In addition, low doses of melatonin induce anticonvulsant action through increase of GABA levels in the hippocampus and brain cortex. The accumulating evidence implicates a modulator role of melatonin on excessive oxidative stress products, plus mitochondrial and Ca 2+ dysregulations in epilepsy. The evidence indicates that modulation of oxidative stress and neuronal Ca 2+ handling occurs through effects on TRP channels, suggesting an increasingly viable approach for therapeutic interventions against epilepsy.

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Anticonvulsant effects of agomelatine in mice

Cited by 37 publications

References 29 publications

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats

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

Role of melatonin on calcium signaling and mitochondrial oxidativestress in epilepsy: focus on TRP channels

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