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Molecular Biology Reports Sep 2023Antiepileptic drugs are versatile drugs with the potential to be used in functional drug formulations with drug repurposing approaches. In the present review, we... (Review)
Review
Antiepileptic drugs are versatile drugs with the potential to be used in functional drug formulations with drug repurposing approaches. In the present review, we investigated the anticancer properties of antiepileptic drugs and interlinked cancer and epileptic pathways. Our focus was primarily on those drugs that have entered clinical trials with positive results and those that provided good results in preclinical studies. Many contributing factors make cancer therapy fail, like drug resistance, tumor heterogeneity, and cost; exploring all alternatives for efficient treatment is important. It is crucial to find new drug targets to find out new antitumor molecules from the already clinically validated and approved drugs utilizing drug repurposing methods. The advancements in genomics, proteomics, and other computational approaches speed up drug repurposing. This review summarizes the potential of antiepileptic drugs in different cancers and tumor progression in the brain. Valproic acid, oxcarbazepine, lacosamide, lamotrigine, and levetiracetam are the drugs that showed potential beneficial outcomes against different cancers. Antiepileptic drugs might be a good option for adjuvant cancer therapy, but there is a need to investigate further their efficacy in cancer therapy clinical trials.
Topics: Neoplasms; Humans; Anticonvulsants; Drug Resistance, Neoplasm; Cell Proliferation; Signal Transduction; Animals
PubMed: 37418080
DOI: 10.1007/s11033-023-08568-1 -
Biomedicines Aug 2023Trigeminal neuralgia (TN) is a unilateral disorder characterized by electric shock-like pain, abrupt onset and termination, and limited to one or more branches of the... (Review)
Review
Trigeminal neuralgia (TN) is a unilateral disorder characterized by electric shock-like pain, abrupt onset and termination, and limited to one or more branches of the trigeminal nerve. Various therapeutic modalities for TN have been introduced. We searched for literature indexed in PubMed, Medline, and the National Library of Medicine and reviewed all relevant articles on non-surgical treatments for TN. Published studies were reviewed with no restrictions on date; reviews, clinical trials, animal studies, retrospective studies, and cases were included. Carbamazepine and oxcarbazepine are the recommended first-line pharmacotherapies. Interventional treatments should be considered when pharmacotherapy is insufficient or withdrawn because of adverse effects.
PubMed: 37626811
DOI: 10.3390/biomedicines11082315 -
Pharmacological Research Mar 2023Despite recent advances in understanding the causes of epilepsy, especially the genetic, comprehending the biological mechanisms that lead to the epileptic phenotype...
Despite recent advances in understanding the causes of epilepsy, especially the genetic, comprehending the biological mechanisms that lead to the epileptic phenotype remains difficult. A paradigmatic case is constituted by the epilepsies caused by altered neuronal nicotinic acetylcholine receptors (nAChRs), which exert complex physiological functions in mature as well as developing brain. The ascending cholinergic projections exert potent control of forebrain excitability, and wide evidence implicates nAChR dysregulation as both cause and effect of epileptiform activity. First, tonic-clonic seizures are triggered by administration of high doses of nicotinic agonists, whereas non-convulsive doses have kindling effects. Second, sleep-related epilepsy can be caused by mutations on genes encoding nAChR subunits widely expressed in the forebrain (CHRNA4, CHRNB2, CHRNA2). Third, in animal models of acquired epilepsy, complex time-dependent alterations in cholinergic innervation are observed following repeated seizures. Heteromeric nAChRs are central players in epileptogenesis. Evidence is wide for autosomal dominant sleep-related hypermotor epilepsy (ADSHE). Studies of ADSHE-linked nAChR subunits in expression systems suggest that the epileptogenic process is promoted by overactive receptors. Investigation in animal models of ADSHE indicates that expression of mutant nAChRs can lead to lifelong hyperexcitability by altering i) the function of GABAergic populations in the mature neocortex and thalamus, ii) synaptic architecture during synaptogenesis. Understanding the balance of the epileptogenic effects in adult and developing networks is essential to plan rational therapy at different ages. Combining this knowledge with a deeper understanding of the functional and pharmacological properties of individual mutations will advance precision and personalized medicine in nAChR-dependent epilepsy.
Topics: Animals; Receptors, Nicotinic; Nicotinic Agonists; Seizures; Phenotype; Epilepsy
PubMed: 36796465
DOI: 10.1016/j.phrs.2023.106698 -
Medicina (Kaunas, Lithuania) May 2022a stroke-like lesion, the morphological equivalent of a stroke-like episode and the hallmark of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes...
OBJECTIVES
a stroke-like lesion, the morphological equivalent of a stroke-like episode and the hallmark of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, have not been reported as manifestations of thiamine deficiency.
CASE REPORT
a 62-year-old man with a history of chronic alcoholism was admitted after a series of epileptic seizures. Upon waking up from the coma, he presented with disorientation, confusion, confabulation, psychomotor agitation, aggressiveness, right hemianopsia, aphasia, and right hemineglect over weeks. Electroencephalography showed a questionable focal status epilepticus over the left hemisphere, responsive to lorazepam and oxcarbazepine. Follow-up electroencephalographies no longer recorded epileptiform discharges. Cerebral magnetic resonance imaging (MRI) revealed T2-/diffusion weighted imaging (DWI) hyperintensity in the left occipito-temporal region that was not congruent to a vascular territory which persisted for at least nine weeks. Since a lactate-peak could be seen in this lesion by magnetic resonance-spectroscopy, this was interpreted as a stroke-like lesion. Since thiamine was reduced, the stroke-like lesion was attributed to thiamine deficiency after the exclusion of differential diseases, including MELAS and status epilepticus. The patient's behavioural and cognitive dysfunctions largely resolved upon vitamin-B1 substitution.
CONCLUSIONS
the case suggests that thiamine deficiency presumably causes mitochondrial dysfunction with cerebrospinal fluid lactic acidosis and a stroke-like lesion mimicking MELAS syndrome. It should be further studied whether nutritional deficits, such as thiamine deficiency, could give rise to secondary stroke-like lesions.
Topics: Acidosis, Lactic; Humans; MELAS Syndrome; Male; Middle Aged; Mitochondrial Encephalomyopathies; Status Epilepticus; Stroke; Thiamine Deficiency; Wernicke Encephalopathy
PubMed: 35630076
DOI: 10.3390/medicina58050660 -
Journal of Neurology Dec 2022Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear. (Review)
Review
BACKGROUND
Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear.
OBJECTIVE
To identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes.
METHODS
We carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia.
RESULTS
We reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment.
CONCLUSIONS
Drug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.
Topics: Adult; Humans; Hyperammonemia; Valproic Acid; Ammonia; Oxcarbazepine; Epilepsy; Risk Factors; Observational Studies as Topic
PubMed: 35907043
DOI: 10.1007/s00415-022-11304-7 -
Frontiers in Pharmacology 2023This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). This is an ambispective,...
This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%-87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Identifier ChiCTR2300074696.
PubMed: 37711169
DOI: 10.3389/fphar.2023.1189058