Ivabradine possesses anticonvulsant and neuroprotective action in mice

Cavalcante, Talita Matias Barbosa; Júnior, José de Maria Albuquerque de Melo; Lopes, Lia Bastos; Bessa, Matheus Costa; Santos, Jéssica Gurgel; Vasconcelos, Luna Costa; Neto, Antônio Eufrásio Vieira; Borges, Lucas Teixeira Nunes; Fonteles, M.M.F.; Filho, Adriano José Maia Chaves; Macêdo, Danielle Silveira; Campos, Adriana Rolim; Aguiar, Carlos Clayton Torres; Vasconcelos, Silvânia Maria Mendes

doi:10.1016/j.biopha.2018.11.096

Cited by 24 publications

(28 citation statements)

References 31 publications

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“…Consistent with previous studies (Cavalcante et al, 2019;Mansour and Ibrahim, 2015;Sawicka et al, 2017a;Sawicka et al, 2017b), ivabradine (10 mg/kg, i.p.) reduced seizure susceptibility, increasing the latency to s.c.PTZ-induced maximal tonic hindlimb extension seizures (Fig.…”

Section: Broad-spectrum Hcn Channel Block Reduced Seizure Susceptibilsupporting

confidence: 92%

“…(Benarroch, 2013;DiFrancesco and DiFrancesco, 2015;Reid et al, 2012). Several previous studies have reported the anticonvulsant properties of the broad-spectrum HCN channel blocker, ivabradine (Cavalcante et al, 2019;Luszczki et al, 2013;Mansour and Ibrahim, 2015). Here we confirm the anticonvulsant properties of ivabradine in the s.c.PTZ seizure assay.…”

Section: The Impact Of Isoform-preferring Hcn Channel Blockers On Seimentioning

confidence: 94%

“…Ivabradine reduces kainic acid-induced seizures in rats (Mansour and Ibrahim, 2015) and increases the threshold of maximal electroshock seizures in mice (Luszczki et al, 2013). In addition, ivabradine has shown anticonvulsive effects in the subcutaneous PTZ (s.c.PTZ) seizure assay J o u r n a l P r e -p r o o f in mice (Cavalcante et al, 2019). The antiseizure effects of ivabradine have also been studied in conjunction with other classical antiepileptic drugs such as lacosamide, pregabalin, lamotrigine, and topiramate within the mouse maximal electroshock (MES) and tonic-clonic seizure models, although determining efficacy is complicated by drug-drug interactions (Sawicka et al, 2017a;Sawicka et al, 2017b).…”

Section: Introductionmentioning

confidence: 99%

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Testing broad-spectrum and isoform-preferring HCN channel blockers for anticonvulsant properties in mice

et al. 2020

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Broad-spectrum Hcn Channel Block Reduced Seizure Susceptibilsupporting

confidence: 92%

Section: The Impact Of Isoform-preferring Hcn Channel Blockers On Seimentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Testing broad-spectrum and isoform-preferring HCN channel blockers for anticonvulsant properties in mice

et al. 2020

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“…74 GABA is the predominant inhibitory amino acid neurotransmitter in the neuronal tissue and its reduction was associated with the development of seizures that also coupled with the blockade of GABA receptors and the inhibition of chloride ions influx resulting in hyperexcitability and neuronal death. 75 Glutamate represents the main excitatory amino acid neurotransmitter in the mammalian brain. The excessive release of glutamate over activates glutamatergic receptors including NMDARs that enhance the development of seizure.…”

Section: Dovepressmentioning

confidence: 99%

<p>Selenium Nanoparticles Pre-Treatment Reverse Behavioral, Oxidative Damage, Neuronal Loss and Neurochemical Alterations in Pentylenetetrazole-Induced Epileptic Seizures in Mice</p>

Yuan¹,

Fu²,

Ji³

et al. 2020

IJN

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Introduction: Epilepsy is a chronic neurological condition characterized by behavioral, molecular, and neurochemical alterations. Current antiepileptic drugs are associated with various adverse impacts. The main goal of the current study is to investigate the possible anticonvulsant effect of selenium nanoparticles (SeNPs) against pentylenetetrazole (PTZ)mediated epileptic seizures in mice hippocampus. Sodium valproate (VPA) was used as a standard anti-epileptic drug. Methods: Mice were assigned into five groups (n=15): control, SeNPs (5 mg/kg, orally), PTZ (60 mg/kg, intraperitoneally), SeNPs+PTZ and VPA (200 mg/kg)+PTZ. All groups were treated for 10 days. Results: PTZ injection triggered a state of oxidative stress in the hippocampal tissue as represented by the elevated lipoperoxidation, heat shock protein 70 level, and nitric oxide formation while decreased glutathione level and antioxidant enzymes activity. Additionally, the blotting analysis showed downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the epileptic mice. A state of neuroinflammation was recorded following the developed seizures represented by the increased pro-inflammatory cytokines. Moreover, neuronal apoptosis was recorded following the development of epileptic convulsions. At the neurochemical level, acetylcholinesterase activity and monoamines content were decreased in the epileptic mice, accompanied by high glutamate and low GABA levels in the hippocampal tissue. However, SeNP supplementation was found to delay the onset and decreased the duration of tonic, myoclonic, and generalized seizures following PTZ injection. Moreover, SeNPs were found to provide neuroprotection through preventing the development of oxidative challenge via the upregulation of Nrf2 and HO-1, inhibiting the inflammatory response and apoptotic cascade. Additionally, SeNPs reversed the changes in the activity and levels of neuromodulators following the development of epileptic seizures. Conclusion: The obtained results suggest that SeNPs could be used as a promising anticonvulsant drug due to its potent antioxidant, anti-inflammatory, and neuromodulatory activities.

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“…Interestingly, the 5-hydroxytryptamine receptor family (e.g., HTR2A, HTR1A, HTR2C, HTR1B, HTR7, HTR3A, etc) and the gamma-aminobutyric acid type A receptor family (e.g., GABRA2, GABRA2, GABRA3, GABRA5) are the most targeted genes by clinically available drugs. In addition, HCN channels which can generate hyperpolarization-activated cation currents and be a causative gene for epilepsy, could also be a potential target tailored as an antiepileptic agent [21,22]. The defect in the KCNJ11 gene (Kir2-encoded current) can also cause convulsive disorder.…”

Section: Ngs For Epilepsy Patientsmentioning

confidence: 99%

Systematic Approach for Drug Repositioning of Anti-Epileptic Drugs

Lee

et al. 2019

Diagnostics

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Epilepsy is a central neurological disorder affecting individuals of all ages and causing unpredictable seizures. In spite of the improved efficacy of new antiepileptic drugs and novel therapy, there are still approximately 20%~30% of patients, who have either intractable or uncontrolled seizures. The epilepsy drug-target network (EDT) is constructed and successfully demonstrates the characteristics and efficacy of popularly used AEDs through the identification of causative genes for 60 epilepsy patients. We discovered that the causative genes of most intractable patients were not the targets of existing AEDs, as well as being very far from the etiological mechanisms of existing AEDs in the functional networks. We show that the existence of new drugs that target the causative genes of intractable epilepsy patients, which will be potential candidates for refractory epilepsy patients. Our systematic approach demonstrates a new possibility for drug repositioning through the combination of the drug-target and functional networks.

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Ivabradine possesses anticonvulsant and neuroprotective action in mice

Cited by 24 publications

References 31 publications

Testing broad-spectrum and isoform-preferring HCN channel blockers for anticonvulsant properties in mice

Testing broad-spectrum and isoform-preferring HCN channel blockers for anticonvulsant properties in mice

<p>Selenium Nanoparticles Pre-Treatment Reverse Behavioral, Oxidative Damage, Neuronal Loss and Neurochemical Alterations in Pentylenetetrazole-Induced Epileptic Seizures in Mice</p>

Systematic Approach for Drug Repositioning of Anti-Epileptic Drugs

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