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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5203_Библиотеки_им_академика_М_И_Перельмана.pdf
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13–06- MG.Their ndings revealed that VGB reduced the activity of intermediateconductance Ca2+-activated K+ (IKCa) channels in the cell adhesion state in a
concentration-dependent manner. DCEBIO could counteract the inhibitory effect of
VGB on IKCa channels. However, VGB did not affect the activity of largeconductance Ca2+-activated (BKCa) channels or inwardly rectifying K+ (KIR)
channels in human 13–06-MG cells. Nonetheless, the addition of GAL-021 or
BaCl2 effectively suppressed BKCa and KIP channels in the presence of VGB.The
results of this study suggested that the inhibition of IKCa channels by VGB may be
a crucial mechanism underlying its antitumor effects, particularly its antiglioma
effects [597].
Commercial immunoassays currently do not include kits for quantifying valproic
acid, vigabatrin, pregabalin, and gabapentin levels without interference from structurally similar substances. Chromatography serves as a viable alternative to immunoassays. Jin P et al. developed a simple, robust nonderivatization gas
chromatography–mass spectrometry method for simultaneously determining the
aforementioned drugs in human plasma. Their method provides reliable drug monitoring during therapy [598].
Vigabatrin, a second-generation ASM, is used for monotherapy in children aged
1month to 2years with spasticity and as an adjunct therapy for adults and pediatric
patients aged 10years and older with intractable complex partial seizures. Optimal
vigabatrin therapy aims for seizure freedom without signicant adverse effects,
with therapeutic drug monitoring (TDM) playing a crucial role. Wang J etal. developed and validated a simple, rapid, and sensitive method for measuring plasma
vigabatrin levels. Their method, which was successfully applied to pediatric patients
undergoing vigabatrin treatment, offers valuable information to clinicians for monitoring hospital plasma vigabatrin levels [599].
2.1.2.9 Zonisamide
Drug Characteristics
[Chemical name] 1,2-Benzisoxazole-3-methanesulfonamide
[Chemical structural formula]
[Molecular formula] C8H8N2O3S
[Molecular weight] 212.23
2 Antiseizure Medications
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[Adaptation to disease] For the treatment of major seizures, minor seizures, localized seizures, status epilepticus and psychomotor seizures.
[Specication] 100mg
[Usage and dosage]
Oral: Adults initially receive 100–200mg daily, divided into one to three oral doses.
Within 1–2weeks, the dosage is increased to 200–400mg daily, divided into one to
three oral doses. The maximum daily dose is 600mg. The initial daily dose for
children is 2–4 mg/kg orally divided one to three times, which is increased to
4–8mg/kg orally divided one to three times within 1–2weeks. The maximum dose
for 1day is 12mg/kg.
[Adverse reactions]
Common symptoms include drowsiness, anorexia, dizziness, headache, nausea, and
anxiety or impatience.
Clinical Application andBasic Research
Historical Evolution ofZonisamide
In 1980, Ito etal. suggested that zonisamide inhibited the activity of epileptogenic
foci in the cortex and blocked the transmission of epilepsy from the cortex to subcortical structures [600]. Since its introduction, zonisamide has been the subject of
ongoing research. In 1985, J.C. Sackellares etal. conducted a study on zonisamide
involving 10 adult patients with intractable partial epilepsy. Their ndings indicated
that substituting the use of standard ASMs with that of zonisamide led to a decrease
in seizure frequency for the majority of patients. Additionally, dose-dependent
reversible side effects were observed in both the central nervous system and gastrointestinal system [601]. These early studies laid the groundwork for the clinical
application of zonisamide in epilepsy treatment. In 1987, E.J. Hammond etal. further discussed the neuropharmacological aspects of zonisamide. Their ndings
from preliminary clinical trials demonstrated the efcacy of the drug against various
seizure types, including generalized tonic–clonic, simple, and complex partial seizures [602]. Since then, zonisamide has been marketed in Japan since 1989 as an
antiseizure medication that acts through multiple mechanisms [603]. In 1996, M K
Ito etal. conducted a study examining the impact of zonisamide on the voltagedependent T-type calcium current (ICa) in cultured human neuroblastoma cells
(NB-I). These ndings suggested that the blockade of T-type calcium channels by
zonisamide could inhibit a critical component of the inward current responsible for
triggering epileptoid cell ring, thereby restraining the propagation of epileptic
activity [604]. This research provides a solid foundation for further electrophysiological investigations of zonisamide and its role in epilepsy management.
Subsequently, the drug received approval for marketing in the United States in 2000
and in Europe in 2005 [603]. In March 2005, zonisamide capsules were authorized
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for sale in the United Kingdom and Germany as adjunctive therapy for treating
partial epileptic seizures, establishing it as a broad-spectrum antiseizure medication
[605]. In 2006, Martin J Brodie published an article suggesting that combining
zonisamide with commonly used ASMs could offer effective and well-tolerated
treatment for patients with intractable partial epilepsy [606]. This is an encouraging
result. In 2015, Saori Tsujii etal. studied the neuroprotective effect of zonisamide
on endoplasmic reticulum stress [607]. These reports indicate that much of the
research on zonisamide is relatively recent. In 2021, Stefano Parravicini et al.
described a case of electroclinical improvement in patients with 20-ring chromosome syndrome following zonisamide treatment. Epilepsy associated with this syndrome is often medically challenging to address. When traditional medications such
as valproate and lamotrigine fail to yield results, zonisamide may merit further
investigation due to its antifocal effect and potential for preventing dopamine depletion [608]. This nding also suggests that combining the pharmacological characteristics of drugs to explore the clinical use of zonisamide to open up new areas is a
sound approach.
Efcacy andSafety ofZonisamide intheAdjuvant Treatment ofRefractory
Epilepsy
A study assessed the efcacy and reliability of zonisamide (ZNS), a novel ASMs, in
children with treatment-resistant epilepsy who were already on multiple ASMs.
Among the participants, 46 (67.6%) had treatment-resistant generalized epilepsy
(RGE), and 22 (32.35%) had treatment-resistant focal epilepsy (RFE). In the RGE
group, 26 patients (56.5%) experienced a reduction in seizures of more than 50%,
and seven patients (15.2%) achieved complete seizure cessation. In the RFE group,
19 patients (86.4%) experienced a reduction in seizures of more than 50%, and two
patients (9.1%) achieved complete seizure cessation. Notably, among patients diagnosed with tuberous sclerosis (TSC) who were followed, four patients experienced
signicant termination or reduction of seizures by more than 50% [605].
Furthermore, Rubio etal. presented the case of a patient who was diagnosed with
Lafora disease and had previously shown a poor response to several ASMs. The
patient exhibited a favorable and stable response to zonisamide, suggesting its
potential as a treatment option for progressive myoclonic epilepsy (MPE) [609].
Application ofZonisamide intheTreatment ofEpilepsy inSpecial Populations
ZNS has emerged as an effective and dependable adjunctive therapy for children
with refractory epilepsy, particularly focal epilepsy, and it may hold promise for
patients with tuberous sclerosis (TSC) [605]. However, concerns have been raised
regarding the potential teratogenicity of zonisamide during human pregnancy. One
study revealed three major congenital malformation (MCM) cases in the ZNS
monotherapy group and ve in the combined treatment group. The median birth
weights for infants in the monotherapy and multidrug groups were 71 and 44
ounces, respectively, and the incidence of small-for-gestational-age babies was
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notably greater (21% for both groups). These ndings warrant attention regarding
the potential teratogenic effects of zonisamide during pregnancy [610]. Rebecca
etal. described the case of a young female patient with global developmental delay,
progressive ataxia, epilepsy, and myoclonus stemming from a truncated mutation in
the SEMA6B gene. Recent research has identied DNA truncation variations in the
last exon of SEMA6B as the cause of autosomal dominant progressive myoclonic
epilepsy. Treatment with zonisamide has shown clinical improvements in patients,
particularly in alleviating both positive and negative myoclonus, along with signicant enhancements in gait and mobility [611].
Application ofZonisamide inOther Diseases
ZNS exhibits benets in patients with obesity and metabolic syndrome who are at
high risk for vascular diseases. One study evaluated the efcacy of ZNS in reducing obesity and mitigating vascular disease and liver steatosis. The hepatic steatosis index (HSI) was used to assess nonalcoholic fatty liver disease progression.
After 12 and 24weeks of ZNS treatment, 24.6% and 32.8% of patients, respectively, experienced a ≥5% loss of body weight. Generalized estimation equation
analysis, adjusting for baseline variables, indicated signicant reductions in body
weight, BMI, serum HbA1c, triglyceride, and hs-CRP levels and HSI scores
[612]. In recent years, zonisamide has been the subject of numerous studies focusing on its potential in Parkinson’s disease (PD) management. Naito etal. conducted a comprehensive transcriptome sequencing analysis of PD patients. They
selected 23 zonisamide hyperresponders (SRs) and 25 nonresponders (NRs) from
among PD patients and analyzed whole-transcriptomic data from peripheral blood
samples before and 12 weeks after zonisamide treatment. Differential gene
expression analysis of SRs and NRs at each time point revealed that the efcacy
of zonisamide in PD patients was correlated with glutamate-related synaptic regulation and p53-mediated dopaminergic nerve loss [613]. Suzuki K. etal. conducted a 3-month open-label study to investigate the effects of zonisamide on
motor symptoms, depressive symptoms, and sleep problems in PD patients.
Patients receiving zonisamide at doses of 25–50mg/day underwent corresponding scale assessments and questionnaire surveys. This study demonstrated signicant improvements in the Parkinson’s Disease Sleep Scale (PDSS-2) score at
3months in the tremor group and in the Beck Depression Inventory-II (BDI-II)
score at 1, 2, and 3months in the nontremor group following zonisamide treatment. These ndings underscore the benecial effects of zonisamide on motor
symptoms and sleep problems in PD patients treated with levodopa experiencing
motor uctuations [614].
Zonisamide has demonstrated efcacy as an adjunct therapy for alleviating
motor symptoms in Parkinson’s disease (PD) patients. Considering that Lewy
body dementia (DLB) and PD are considered subtypes of Lewy body spectrum
disorders, zonisamide was investigated for treating Parkinson’s symptoms in
DLB patients. In Japanese phase II and phase III clinical trials involving DLB
patients, participants were randomly assigned to receive zonisamide at doses of
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25 or 50mg/day or placebo for 12weeks. The results revealed that zonisamide
signicantly improved the Unied Parkinson’s Disease Rating Scale Part III
(UPDRS-III) score without affecting cognitive or neuropsychiatric measures at
week 12 [615]. Moreover, Manabu etal. conducted a study to compare the efcacy and safety of adding zonisamide (25mg/day) versus increasing levodopa
doses (100mg/day but ≤300mg/day) in treating Parkinson’s syndrome in DLB
patients. At weeks 16 and 24, the adjusted mean change in the Movement
Disorder Society Unied Parkinson’s Disease Rating Scale Part III (MDSUPDRS Part III) total score was signicantly greater in the zonisamide addition
group than in the levodopa dose increase group. These ndings suggest that in
DLB patients with insufcient levodopa efcacy, the addition of zonisamide
(25 mg/day) can moderately improve motor symptoms. However, it remains
uncertain whether the addition of zonisamide (25 mg/day) is as effective as
increasing the levodopa dose (100mg/day) [616]. Furthermore, a meta-analysis
indicated that zonisamide can enhance motor function in both PD patients and
DLB patients, improve activities of daily living and drug efcacy in PD patients,
and shorten the duration of motor disorders. These ndings collectively support
the potential role of zonisamide as a benecial treatment option for motor symptoms in PD and DLB patients [617].
Zhengguang Wang etal. conducted a study utilizing 40 adult Sprague–Dawley
rats to establish a model of degenerative cervical spondylitic myelopathy (DCM).
The rats were divided into four groups: the Sham group, the DCM model group, the
ZNS group (treated with zonisamide), and the ZNS+CD95 group. Their ndings
indicated that ZNS treatment facilitated motor recovery and reversed the histopathological injuries and apoptosis observed in DCM rats. Additionally, ZNS was
observed to mitigate DCM damage by regulating Fas and FasL signaling, suggesting its benecial effect on DCM [618].
In a study by Rose JE etal., a novel treatment approach involving the combination of bupropion and zonisamide was explored to aid smokers in transitioning
from combustible cigarettes (CCs) to electronic nicotine delivery systems
(ENDSs). Twenty-four smokers participated in a 13-week treatment regimen in
which they were provided ENDSs, bupropion, and zonisamide. The assessment
parameters included CC and ENDS usage, exhaled air carbon monoxide (CO)
levels, smoking cessation symptoms, reward scores, and tolerance/side effects. At
the conclusion of the study, 33% of participants achieved biochemically conrmed complete abstinence from CCs, indicating the potential efcacy of the
bupropion/zonisamide combination in facilitating the transition to ENDSs. This
suggests that further randomized controlled trials are warranted to validate this
promising approach [619].
Side Effects ofZonisamide
Zonisamide can cause delirium through toxic epidermal necrolysis (TEN) [620].
TEN and Stevens-Johnson syndrome (SJS) are life-threatening reactions marked by
extensive skin stripping and mucosal erosion. Samuel etal. described a case of TEN
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accompanied by delirium and psychosis triggered by zonisamide. Zonisamide has
been linked to psychosis and other mental disorders, particularly when it is used
concomitantly with other ASMs. For instance, a 61-year-old woman diagnosed with
heparin-induced SJS experienced worsening insomnia, persecution delusions, and
visual hallucinations.
Pj nar Ozkan Kart etal. examined the histological effects of ZNS and other
commonly used ASMs on rat ovarian tissue. ZNS, along with STM, LCM,
CLB, and RUF, administered to nonepileptic preadolescent rats had adverse
effects on ovarian tissue follicular ability when continued into adulthood.
ZNS treatment led to a significant reduction in the number of atretic follicles
and corpus luteum in the ovaries, along with an increase in the number of
apoptotic follicles. Animal studies suggest potential teratogenic effects and a
risk of miscarriage associated with zonisamide use [534]. Furthermore,
zonisamide has been linked to decreased appetite and weight loss in children,
potentially leading to underlying health issues and poor treatment adherence
[80]. Additionally, a case involving a woman in her 20s who developed distal
(type 1) renal tubular acidosis due to zonisamide, resulting in severe hypokalemia, corrected QT interval prolongation, and metabolic acidosis, has been
reported [621]. Regarding safety concerns, zonisamide use significantly
increases the likelihood of contusion in patients with dementia with Lewy
bodies (DLB) and may also cause appetite loss in DLB patients and drowsiness in Parkinson’s disease (PD) patients [617].
Evidence-Based Medical Research onZonisamide
A meta-analysis of zonisamide for epileptic spasticity, comprising studies with at
least 10 participants, included 401 children with epileptic spasms. They were
administered ZNS at doses ranging from 9.9 to 35mg/kg/day, with few patients
experiencing minor adverse effects. The results indicated that 20.8% (95%
CI-11.4–29.2%) and 23.4% (95% CI-17.8–29.1%) of patients treated with
zonisamide achieved complete cessation of spasticity and at least a 50% reduction
in total spasticity frequency compared to baseline, respectively. Additionally, 20.3%
(95% CI-10.1–30.5%) of patients exhibited alleviation of EEG rhythms with
zonisamide. These ndings demonstrate that zonisamide can effectively reduce
spasticity in approximately 21% of children with epilepsy, with minimal adverse
reactions [622].
Basic Research onZonisamide
Zonisamide upregulates neuregulin-1 expression and enhances acetylcholine
receptor aggregation at neuromuscular junctions invitro, enhancing the axonal elongation of primary spinal motor neurons (SMNs). Taro et al. investigated the impact of ZNS on AChR clusters at NMJs, given the compensatory
role of neuroblastulation in human diseases involving AChR cluster loss. The
authors observed that molecules conferring ZNS responsiveness were not
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secreted into the medium. Moreover, while 10 μM ZNS upregulated Nrg1
expression in cocultured cells, it had no effect on monocultures of C2C12
muscle tubes or NSC34 motor neurons. Inhibition of the Nrg1/ErbB signaling
pathway counteracted the enhancement of AChR clustering induced by 10μM
ZNS treatment in NMJs in vitro, and antiagglomerin antibodies mitigated
ZNS-mediated AChR clustering enhancement [623]. Zonisamide exhibits a
neuroprotective effect on adult rat dorsal root ganglion (DRG) neurons
invitro, countering the toxic effects of the platinum-based drug oxaliplatin
(OHP), which is known to induce peripheral neuropathy. Pretreatment with
zonisamide (100μM) significantly reduced OHP-induced death of DRG neurons. Additionally, zonisamide inhibited p38 MAPK phosphorylation in
ND7/23 DRG neurons treated with OHP.This neuroprotection against OHPinduced peripheral sensory neuropathy may involve the activation of the MEK/
ERK and PI3K/AKT signaling pathways and the concurrent inhibition of the
p38 MAPK pathway in DRG neurons [624]. Using an inflammatory astrogliamicroglia coculture model, Ismail FS and colleagues investigated the effects
of tiagabine (TGB) and zonisamide (ZNS). They investigated glial cell viability, microglial activation, articulin 43 (Cx43) expression, and the coupling of
gap junctions. These findings indicate that under inflammatory conditions,
TGB exhibits potential anti-inflammatory effects. Conversely, ZNS did not
significantly alter the microglial phenotype. Moreover, ZNS might exert supplementary antiseizure effects by interfering with glial gap junction communication during inflammatory states. Notably, there were disparities in the
modulation of glial cell characteristics between the TGB and ZNS groups
[625]. Tada et al. established a PD mouse model through treatment with
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and lipopolysaccharide (LPS).
Their aim was to explore the impact of zonisamide on mitochondrial reactive
oxygen species generation in microglia. Zonisamide reversed the inhibitory
effects of LPS on the mitochondrial oxygen consumption rate (OCR), providing insights into mitigating mitochondrial dysfunction in microglia. This finding supports its potential clinical utility as a treatment for Parkinson’s disease
[618]. Idiopathic epilepsy (IE) is a prevalent chronic brain disorder in canines.
Recent investigations into the efficacy of a medium-chain triglyceride (MCT)rich diet on seizure frequency in dogs with IE have been conducted. These
studies revealed no significant difference in episode frequency between dogs
fed a placebo diet (PL) and those fed a Purina ProPlan Veterinary Diet
Neurocare (NC) diet. Moreover, concurrent administration of zonisamide
alongside the MCT diet did not cause any discernible adverse effects and did
not influence the zonisamide concentration. Hence, commercially available
MCT-rich diets (NCs) can be safely administered concurrently with zonisamide
to IE-afflicted dogs [626].
2 Antiseizure Medications
2.1.3 Third-Generation Antiseizure Medications
2.1.3.1 Lacosamide
Medicinal Features
[Chemical name] (R)-2-(acetylamino)-N-benzyl-3-methoxypropionamide
[Structure formula]
227
[Molecular formula] C13H18N2O
3
[Molecular weight] 250.30
[Indications] Monotherapy or add-on therapy in the treatment of partial-onset sei-
zures in patients with epilepsy aged 4years and older.
[Dosage forms]
Film-coated tablets: 50mg/100mg/200mg
Oral solution: 200mL (2g)
Injection: 200mg
[Dosage and administration]
Adults (aged 17 and above) and children weighing ≥50kg:
Treatment begins with a dosage of 50mg per administration, which is administered twice daily. The dose is incrementally increased weekly to 50mg per administration, twice daily, until the maximum permissible dosage of 400mg/day is
reached.
Pediatric and adolescent patients (aged 4years and above):
Pediatric patients weighing 30–50kg: Initiate treatment at 1mg/kg per administration, twice daily. The dosage is adjusted weekly to 1mg/kg, following a twicedaily regimen, up to a maximum of 8mg/kg/day.
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Pediatric patients weighing ≥11 to <30kg: Commence with a dosage of 1mg/kg
per administration, twice a day. The dose is increased weekly by 1mg/kg, adhering
to a twice-daily schedule, with a maximum dosage of 12mg/kg/day.
[Adverse effects]
Dizziness, nausea, diplopia, vomiting, fatigue, blurred vision, ataxia, tremor, etc.
[Historical evolution]
Lacosamide (LCM) is a synthetically manufactured antiseizure medication (ASM).
It selectively enhances the slow inactivation of voltage-gated sodium channels without affecting rapid inactivation. Its antiepileptic mechanism is also associated with
interactions with collapsin response mediator protein (CRMP-2) [627]. In 2008, the
FDA approved it for adjunctive therapy in focal epilepsy in patients aged 17 and
older [628]. Initially, approved for adjunctive therapy, it subsequently received
approval for monotherapy indications, extending from adult patients to children and
adolescents aged 4years and above.
Inoue Y. et al. [629] conducted a phase III, long-term, open-label extension
(OLE) trial to evaluate the long-term safety, tolerability, and efcacy of adjunctive
lacosamide (100–400mg/day) in Chinese and Japanese people with epilepsy (PWE)
(16–70years) who had completed a double-blinded, randomized, placebo- controlled
trial of adjunctive lacosamide. The median reduction in focal seizure frequency per
28days from baseline was 57.1%, and the ≥50% and ≥75% responder rates were
57.1% (269/471) and 29.7% (140/471), respectively. Among people with epilepsy
(PWE) who completed 12, 24, and 36 months of treatment, the 12-, 24-, and
36-month seizure-free survival rates were 3.5% (13/375), 3.4% (11/321), and 2.0%
(5/247), respectively. The most common treatment-emergent adverse events (≥20%
of PWE) were nasopharyngitis, dizziness, and upper respiratory tract infection.
In a phase III, double-blinded, noninferiority trial [630], newly diagnosed adult
patients were randomly assigned to receive either controlled-release CBZ or monotherapy with lacosamide, with daily doses of LCM ranging from 200 to 600mg. By
comparing metrics such as the proportion of patients who were seizure-free at
6months and the incidence of adverse events, researchers considered lacosamide to
be a rst-line monotherapy for newly diagnosed epilepsy. Another phase III, doubleblinded, randomized, placebo-controlled trial [631] included 242 patients (≥4years
old) with idiopathic generalized epilepsy (IGE) with poorly controlled primary generalized tonic–clonic seizures (PGTCS). Compared with placebo, lacosamide signicantly differed in terms of the risk of GTCS recurrence within 24 weeks,
seizure-free rates at 24weeks, and reduction in GTCS frequency.
Fundamental andClinical Research onLacosamide
Recent Fundamental Research
Studies on the mechanism of lacosamide have focused on its antioxidative and antiinammatory protective effects. Lazzarotto, L. etal. [632] investigated the effects of
LCM on biochemical and mitochondrial parameters in mice using a PTZ-induced
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229
model. These changes included changes in expression levels of superoxide dismutase
(SOD), catalase (CAT), mitochondrial complexes, Bcl-2, and cyclooxygenase- 2
(COX-2). These results suggest that while LCM does not inhibit seizure generation
invivo, it offers neuroprotection against oxidative stress, bioenergetic dysfunction, and
DNA damage. Bilal B etal. [633] studied the neuroprotective effects of lacosamide in a
rat model of Parkinson’s disease and showed that drug intervention signicantly reduced
dopaminergic neuron degeneration, decreased malondialdehyde and inammatory
cytokine (TNF-α) levels, and increased dopamine metabolite (HVA) abundance.
Langton RL etal. [634] reported that lacosamide inhibited neocortex epileptiform discharges in neonatal mice without increasing neuronal apoptosis. Other
researchers [635] have evaluated the effect of LCM on kynurenine pathway (KP)
levels in a mouse model of epilepsy with comorbid depression based on measurements of inammatory cytokines and oxidative stress markers. They concluded that
the antiepileptic effect of LCM is at least partly due to its anti-inammatory and
antioxidative activities. Corvace F. and colleagues [636] concluded that LCM has
no signicant effect on glial cell activity, and its induced reduction in gap junction
protein expression may be related to its antiepileptic activity. LCM also reduced the
number of activated microglia, thereby decreasing neuroinammatory responses
and reducing the likelihood of epilepsy.
In regard to status epilepticus (SE), Szewczyk A. et al. [637] used pilocarpine
(PILO) to induce SE in mice and assessed the impact of the drug on neurogenic
stem cell (NSC) proliferation and cognitive functions. They found that long-term
treatment with LCM appeared to have no negative impact on cognitive function or
neurogenesis. However, prolonged usage of LCM might reduce the formation of
new neurons. Shishmanova-Doseva M. etal. [449] also used a pilocarpine-induced
model to determine that the antioxidative mechanisms of LCM and TPM might
contribute to their anticonvulsant effects. Sumbul O. etal. [638] used an animal
model of penicillin-induced status epilepticus to evaluate the electrophysiological
and biochemical effects of lacosamide. Lower doses of lacosamide (10mg/kg) signicantly reduced spike wave frequency, decreased ST-segment elevation to the
level of the control group and inhibited the increase in total oxidant status (TOS)
and TNF-α levels, while higher doses of LCM (50mg/kg) not only increased spike
wave frequency but also increased ST-segment elevation and the QT and PR
intervals.
+
Wu PM etal. [639] explored the effects of lacosamide on voltage-gated Na
currents (INas). They found that lacosamide inhibited both the peak and sustained
components of INas and could alter their magnitudes, gating, and voltage dependency, possibly via postbinding interactions with certain amino acid residues in
sodium channels.
Application inCritical Care
Among third-generation ASMs, lacosamide is advantageous because of its increasing application in status epilepticus, cluster seizures, and other critical conditions,
making it a treatment for convulsive status epilepticus (CSE) with broad application
prospects [640].