Anticonvulsant effects of mefloquine on generalized tonic-clonic seizures induced by two acute models in rats

Franco-Pérez, Javier; Ballesteros-Zebadúa, Paola; Manjarrez-Marmolejo, Joaquín

doi:10.1186/s12868-015-0145-7

Cited by 19 publications

(12 citation statements)

References 33 publications

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“…The degree of sedation and seizure behavior of the mice were recorded and assessed for 1 hour after PTZ administration. The anticonvulsive effects of LMR‐101 in this study were also evaluated using a rat model in which seizures were induced by administration of 70 mg/kg (close to CD97 for Sprague‐Dawley rats) PTZ (methods and results are shown in Appendix ) 17 …”

Section: Methodsmentioning

confidence: 99%

LMR‐101, a novel derivative of propofol, exhibits potent anticonvulsant effects and possibly interacts with a novel target on γ‐aminobutyric acid type A receptors

Zhao

Guo

et al. 2021

Epilepsia

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ObjectiveLMR‐101 is a bisphenol derivative of propofol, a short‐acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR‐101 to discover its potential to manage epilepsy and SE in the clinic.MethodsComparative studies between LMR‐101 and propofol were performed in mice to elucidate an appropriate dose range for LMR‐101 that produced anticonvulsant effects without significant sedation. Then, the anticonvulsive efficacy for LMR‐101 was evaluated using seizure models induced by pentylenetetrazol and (+)‐bicuculline. The ability of LMR‐101 to inhibit SE was assessed using a rat model of SE induced by pilocarpine. Radioligand binding assay profiles for LMR‐101 were performed to evaluate the potential mechanisms of action underlying its anticonvulsant properties.ResultsIn the mouse study, LMR‐101 exhibited greater anticonvulsant and lesser sedative effect compared with propofol. LMR‐101 completely inhibited pentylenetetrazol‐induced seizures at a dose of 50 mg/kg and exhibited heavy sedation at 300 mg/kg. Propofol anesthetized all mice and only decreased the seizure rate at 25 mg/kg. LMR‐101 also suppressed seizure behaviors evoked by (+)‐bicuculline in mice in a dose‐dependent manner. In the pilocarpine‐induced SE model, LMR‐101 significantly decreased the maximum seizure score and seizure duration in a dose‐dependent manner. The median effective dose for LMR‐101 was 14.30 mg/kg and 121.87 mg/kg to prevent and inhibit sustained SE, respectively. In binding assays, LMR‐101 primarily inhibited tert‐[35S] butylbicyclophosphorothionate binding to γ‐aminobutyric acid type A (GABAA) receptors (half‐maximal inhibitory concentration = 2.06 μmol·L–1), but it did not affect [3H] flunitrazepam or [3H] muscimol binding.SignificanceIt is anticipated that LMR‐101 might play an essential role in the clinical management of epilepsy and SE. LMR‐101 also might bind to a novel target site on the GABAA receptor that is different from existing antiepileptic drugs. Further study of the mechanisms of action of LMR‐101 would be of considerable value in the search for new active drug sites on GABAA receptors.

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Section: Methodsmentioning

confidence: 99%

LMR‐101, a novel derivative of propofol, exhibits potent anticonvulsant effects and possibly interacts with a novel target on γ‐aminobutyric acid type A receptors

Zhao

Guo

et al. 2021

Epilepsia

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“…Indeed, it has been shown that GJ blockers such as carbenoxolone (165)(166)(167), mefloquine (168), quinine (166,167,169), and quinidine (170) alleviate seizure severity in various animal models of epilepsy, although a general consensus on the exact mode of action and the efficacy of these compounds is still lacking. Anandamide and oleamide are fatty acids of the endocannabinoid family that have been demonstrated to inhibit intercellular GJs from glial cells (171,172).…”

Section: Gap Junctionsmentioning

confidence: 99%

“…Furthermore, panx-1 in conjunction with P 2 X7R potentiates seizure activity in an animal model of epilepsy as well as in brain slices of patients with TLE (252). Panx-1 channels are exciting new targets as global panx-1 inhibition has anticonvulsive effects in animal models of epilepsy (168,251).…”

Section: Ca 2+ -Independent Mechanisms Of Gliotransmitter Releasementioning

confidence: 99%

Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis

et al. 2020

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Astrocytes are key homeostatic regulators in the central nervous system and play important roles in physiology. After brain damage caused by e.g., status epilepticus, traumatic brain injury, or stroke, astrocytes may adopt a reactive phenotype. This process of reactive astrogliosis is important to restore brain homeostasis. However, persistent reactive astrogliosis can be detrimental for the brain and contributes to the development of epilepsy. In this review, we will focus on physiological functions of astrocytes in the normal brain as well as pathophysiological functions in the epileptogenic brain, with a focus on acquired epilepsy. We will discuss the role of astrocyte-related processes in epileptogenesis, including reactive astrogliosis, disturbances in energy supply and metabolism, gliotransmission, and extracellular ion concentrations, as well as blood-brain barrier dysfunction and dysregulation of blood flow. Since dysfunction of astrocytes can contribute to epilepsy, we will also discuss their role as potential targets for new therapeutic strategies.

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“… 87 One of the effects of mefloquine in the nervous system is to block gap junction synapses. 88 Nevertheless, because the phenytoin study cited was a single clinical case study (a 26-year-old male), its reliability is discrete. 86…”

Section: The Interactions Between Gabapentin and Other Drugsmentioning

confidence: 99%

Review about gabapentin misuse, interactions, contraindications and side effects

Quintero¹

2017

JEP

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The current work is targeted to review the risks of gabapentin misuse, its potential interactions with other drugs, side effects and use contraindications. This review consists of a total of 99 biographical references (from the year 1983 to 2016). A publication search of PubMed was performed from January 1983 to December 2016. It included animal studies, clinical studies, case studies and reviews related to gabapentin misuse, potential interactions, side effects and use contraindications. The search terms were gabapentin, anticonvulsant and antiepileptic. In general, it seems that gabapentin has risks of being misused based on the increased level of prescriptions, related fatalities, recreational misuse and higher doses of self-administration. The main reasons for gabapentin misuse are as follows: getting high, alleviating opioid withdrawal symptoms and potentiating methadone effects. Some of the main substances that interact with gabapentin are morphine, caffeine, losartan, ethacrynic acid, phenytoin, mefloquine and magnesium oxide. Some of the side effects caused by gabapentin are teratogenicity, hypoventilation, respiratory failure and myopathy. Finally, reports in general contraindicate the use of gabapentin in conditions such as myasthenia gravis and myoclonus.

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Anticonvulsant effects of mefloquine on generalized tonic-clonic seizures induced by two acute models in rats

Cited by 19 publications

References 33 publications

LMR‐101, a novel derivative of propofol, exhibits potent anticonvulsant effects and possibly interacts with a novel target on γ‐aminobutyric acid type A receptors

LMR‐101, a novel derivative of propofol, exhibits potent anticonvulsant effects and possibly interacts with a novel target on γ‐aminobutyric acid type A receptors

Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis

Review about gabapentin misuse, interactions, contraindications and side effects

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