Ethosuximide-loaded bismuth ferrite nanoparticles as a potential drug delivery system for the treatment of epilepsy disease. Encapsulating antiepileptic drugs (AEDs), including ethosuximide (Etho), into nanoparticles shows promise in treating epilepsy. Nanomedicine may be the most significant contributor to addressing this issue. It presents several advantages compared to traditional drug
Ethosuximide lowers lamotrigine serum concentrations: Evidence for a clinically relevant interaction. We investigated the effect of comedication with ethosuximide (ESM) on lamotrigine (LTG) blood levels. Based on observations from clinical practice, we hypothesized that ESM reduces the LTG serum concentration. We additionally evaluated this effect in the presence of concomitant valproic acid (VPA
Model-Informed Precision Dosing Guidance of Ethosuximide Developed from a Randomized Controlled Clinical Trial of Childhood Absence Epilepsy. Ethosuximide was identified as the optimal option for new-onset childhood absence epilepsy (CAE) in a randomized, two-phase dose escalation comparative effectiveness trial of ethosuximide, lamotrigine, and valproic acid. However, 47% of ethosuximide initial monotherapy participants experienced short-term treatment failure. This study aimed to characterize the initial monotherapy ethosuximide exposure-response relationship and to propose model-informed precision dosing guidance. Dose titration occurred over a 16-20-week period until patients experienced seizure freedom or intolerable side effects. Subjects with initial monotherapy failure were randomized to one
An innovative ethosuximide granule formulation designed for pediatric use: Comparative pharmacokinetics, safety, tolerability, and palatability profile versus reference syrup. Ethosuximide, the first-line therapy for childhood absence epilepsy, is currently formulated as a syrup (Zarontin®, Pfizer) with a bitter taste and high sugar content, poorly adapted to children, and a ketogenic diet . The collaborative European FP7 project KIEKIDS aimed at developing an innovative sugar-free, tasteless formulation convenient for pediatric use. This dual Phase-I study evaluated two granule formulations based on lipid multiparticulate (LMP) technology. Two panels of 6 healthy adult volunteers underwent a randomized, placebo-controlled, partly blinded, 3-way cross-over trial, comparing ethosuximide granules
Open-label pilot study of ethosuximide as adjunctive therapy for relieving abdominal pain related to Irritable Bowel Syndrome. There is clear evidence for an association between irritable bowel syndrome (IBS) and visceral hypersensitivity. This clinical study aimed to assess the adjunct role of ethosuximide, an antiepileptic drug with T-type calcium channel blocking activity, in the relieving of IBS-related abdominal pain. This is a prospective, 3-month, randomized and controlled study of parallel groups. Fifty outpatients who met the inclusion criteria participated in the trial. Patients were allocated randomly: 25 received mebeverine 135 mg three times daily (t.i.d), whereas the other 25 received mebeverine 135 mg t.i.d and ethosuximide 500 mg t.i.d. At baseline and 12 weeks after
A Potential Role of Ethosuximide and Pentoxifylline in Relieving Abdominal Pain in Irritable Bowel Syndrome Patients Treated with Mebeverine: A Randomized, Double-Blind, Placebo-Controlled Trial. Irritable bowel syndrome (IBS) is defined as an association of chronic abdominal pain with bowel habit abnormalities, without clear organic dysfunction. T-type calcium channels and low-grade mucosal inflammation are linked to abdominal pain; however, medical treatments for IBS abdominal pain are largely ineffective. In this study, we investigated if pentoxifylline (PTX) and ethosuximide could potentially alleviate abdominal pain in patients with IBS treated with mebeverine. We recruited 150 patients from Tanta University Hospital to this randomized, prospective, and double blinded study. Patients were
Severe Raynaud's phenomenon from ethosuximide raised concern over possible onset of systemic vasculitis: a case report. Ethosuximide and other anti-epileptic drugs have been reported to cause idiosyncratic reactions such as lupus-like syndromes, with elevated antinuclear antibody (ANA) levels. Herein, we present a case of a girl who developed a very severe Raynaud's phenomenon reaction and anti -Scl-70 antibodies related to treatment with ethosuximide, due to juvenile absence epilepsy (JAE). A 12-year-old girl was diagnosed with JAE and treatment with ethosuximide was initiated. Two and a half months later her fingers, digits II-V bilaterally, began to ache and were discolored, alternatingly white, blue, or normal-colored. Two weeks later, her fingers were bluish-black, aching severely
Efficacy of anticonvulsant ethosuximide for major depressive disorder: a randomized, placebo-control clinical trial. Results of a preclinical study suggested that the anticonvulsant drug ethosuximide may elicit ketamine-like rapid-acting antidepressant actions. We evaluated the antidepressant efficacy of ethosuximide versus placebo in non-medicated adult patients with major depressive disorder (MDD). This randomized, double-blind, placebo-controlled trial included patients at three mental health centers in China. Eighty eligible adults (aged 18-65 years) met the DSM-5 criteria for MDD. Patients in the acute single study received three doses (500, 1000, or 1500 mg) of ethosuximide or placebo. Patients in the repeated study received ethosuximide (1500 mg/day) or placebo for 2 weeks
Ethosuximide An official website of the United States government Here's how you know Log inAccess keysNCBI HomepageMyNCBI HomepageMain ContentMain NavigationBookshelfSearch databaseBooksAll DatabasesAssemblyBiocollectionsBioProjectBioSampleBooksClinVarConserved DomainsdbGaPdbVarGeneGenomeGEO DataSetsGEO ProfilesGTRHomoloGeneIdentical Protein GroupsMedGenMeSHNLM and EffectsSummary of Use during LactationAverage ethosuximide dosages of 50 to 60% of the maternal weight-adjusted dosage are excreted in human milk and infant plasma levels of 25 to 30% of maternal levels are common. Although no adverse effects attributable solely to ethosuximide in breastmilk have been reported, monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially
A statistical analysis plan for a randomized clinical trial to evaluate the efficacy and safety of ethosuximide in patients with treatment-resistant depression. A recent striking advance in the treatment of depression has been the finding of rapid antidepressant effects in over 70% of patients with treatment-resistant depression (TRD) using ketamine. However, the potential risk of addiction may limit its clinical use. Recent research revealed that blockade of N-methyl-D-aspartate receptor (NMDAR) dependent bursting activity in the lateral habenula (LHb) could mediate the fast antidepressant effects of ketamine. Further, LHb bursting plays an important role in the pathophysiology of depression that requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Ethosuximide
Lack of Antidepressant Effects of Low-Voltage-Sensitive T-Type Calcium Channel Blocker Ethosuximide in a Chronic Social Defeat Stress Model: Comparison with (R)-Ketamine A recent study demonstrated that low-voltage-sensitive T-type calcium channel blocker ethosuximide shows rapid antidepressant actions. This study was conducted to compare the antidepressant actions of ethosuximide and (R )-ketamine in a chronic social defeat stress model. Ethosuximide (100, 200, or 400 mg/kg), (R)-ketamine (10 mg/kg), or saline was administered i.p. to chronic social defeat stress-susceptible mice. Subsequently, locomotion test, tail suspension test, forced swimming test, and 1% sucrose preference test were performed. (R)-ketamine showed rapid and long-lasting antidepressant actions in chronic social
Assessment of the effectiveness and safety of ethosuximide in the treatment of abdominal pain related to irritable bowel syndrome - IBSET: protocol of a randomised, parallel, controlled, double-blind and multicentre trial. Irritable bowel syndrome (IBS) is characterised by the association of abdominal chronic pain with bowel habit disorders in the absence of identifiable organic disease . The mechanisms causing IBS symptoms are unknown. Recent studies have shown the involvement of T-type channel in abdominal pain. We aim to evaluate the therapeutic potential of ethosuximide, a T-type channel blocker, on the abdominal pain of patients presenting an IBS. The IBSET trial is a randomised, controlled, parallel, double-blind and multicentre study. It is the first clinical trial evaluating
Otoprotective effects of ethosuximide in NOD/LtJ mice with age-related hearing loss Despite long-term efforts to elucidate the mechanisms responsible for age-related hearing loss (AHL), there is currently no available treatment strategy able to provide a cure. Apoptotic cell death, including that of hair cells and spiral ganglion neurons (SGNs) in the cochlea has been proposed to be the classic theory behind the development of AHL. As calcium signaling plays key roles in signal transduction in apoptosis, in this study, we selected ethosuximide, which is able to block T-type calcium (Ca2+ion) channels, suppressing Ca2+. We hypothesized that the apoptotic pathway may be blocked through the inhibition of T-type Ca2+ channels in cochlear cells in NOD/LtJ mice. NOD/LtJ mice were divided into 2
Assessment of the effectiveness and safety of Ethosuximide in the Treatment of non-Diabetic Peripheral Neuropathic Pain: EDONOT-protocol of a randomised, parallel, controlled, double-blinded and multicentre clinical trial. Currently available analgesics are ineffective in 30-50% of patients suffering from neuropathic pain and often induce deleterious side effects. T-type calcium channel blockers (mibefradil, ethosuximide, NNC 55-0396) are of great interest for the development of new symptomatic treatments of neuropathic pain, due to their various effects on pain perception. Interestingly, ethosuximide, which has already been approved for treating epilepsy, is available on the European market for clinical use. Despite numerous preclinical data demonstrating an antinociceptive effect of ethosuximide
Ethosuximide for Essential Tremor: An Open-Label Trial T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2
Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer’s disease mouse model Recent studies have shown that several strains of transgenic Alzheimer's disease (AD) mice overexpressing the amyloid precursor protein (APP) have cortical hyperexcitability, and their results have suggested that this aberrant network activity may be a mechanism by which amyloid-β (Aβ) causes electrodes, and epileptiform activity was correlated with spatial memory function and transgene-specific pathology. The antiepileptic drugs ethosuximide and brivaracetam were tested for their ability to suppress epileptiform activity and to reverse memory impairments and synapse loss in APP/PS1 mice. We report that in two transgenic mouse models of AD (APP/PS1 and 3xTg-AD), the presence of spike-wave
Comparison of the Effects of Zonisamide, Ethosuximide and Pregabalin in the Chronic Constriction Injury Induced Neuropathic Pain in Rats Evidence has been generated that various anticonvulsant agents provide relief of several chronic pain syndromes and therefore as an alternative to opioids, nonsteroidal anti-inflammatory, and tricyclic antidepressant drugs in the treatment of neuropathic pain particular mechanistic classes of anticonvulsants are analgesic. The study included zonisamide, ethosuximide and pregabalin. All compounds were anticonvulsant with diverse mechanism of actions. The peripheral neuropathic pain was induced by chronic constriction injury of the sciatic nerve in male Sprague-Dawley rats. Zonisamide (80 and 40 mg/kg), ethosuximide (300 and 100 mg/kg), pregabalin (50 and 20 mg
Chronic intrathecal infusion of mibefradil, ethosuximide and nickel attenuates nerve ligation-induced pain in rats. T-type Ca(2+) channels (TCC) are important for pain transmission, especially the Ca(V)3.2 subtype. In this study, we examined the effects of intrathecal TCC blockers in the L5/6 spinal nerve ligation pain rat model. Under isoflurane anaesthesia, rats received right L5/6 spinal nerve ligation and intrathecal catheters (attached to an infusion pump) were sited. After surgery, saline, mibefradil, ethosuximide or NiCl2 were given intrathecally for seven days. The right hindpaw withdrawal thresholds to von Frey hair stimuli and withdrawal latencies to radiant heat were measured before and once daily for seven days after surgery. Double immunofluorescence and western blotting
Ethosuximide Affects Paired-Pulse Facilitation in Somatosensory Cortex of WAG\Rij Rats as a Model of Absence Seizure The interaction between somatosensory cortex and thalamus via a thalamocortical loop is a theory behind induction of absence epilepsy. Inside peri-oral somatosensory (S1po) and primary somatosensory forelimb (S1fl) regions, excitatory and inhibitory systems are not balanced and GABAergic inhibitory synapses seem to play a fundamental role in short-term plasticity alterations. We investigated the effects of Ethosuximide on presynaptic changes by utilizing paired-pulse stimulation that was recorded from somatosensory cortex in 18 WAG\Rij rats during epileptic activity. A twisted tripolar electrode including two stimulating electrodes and one recording electrode was implanted
Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound hyperexcitability can result in withdrawal seizure. Withdrawal symptoms, including seizures, may drive individuals to relapse, thus representing a significant barrier to recovery. Our lab previously identified an upregulation of the thalamic T-type calcium (T channel) isoform CaV3.2 as a potential contributor to the generation and propagation of seizures in a model of withdrawal. In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity. DBA/2J mice were