A mechanistic approach to explore the neuroprotective potential of zonisamide in seizures

Kumar, Bobbala Ravi; Modi, Manish; Saikia, Biman; Attri, Savita Verma; Patial, Ajay

doi:10.1007/s10787-018-0478-9

Cited by 13 publications

(9 citation statements)

References 30 publications

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“…Major depression has been observed as the most common side effect of zonisamide drug discontinuation [ 39 ]. Signs of oxidative stress in testicular tissue due to decreased catalase activities and increased malondialdehyde levels have also been observed in the zonisamide treated patients, which suggest the possibility of male reproductive toxicity as a side effect of zonisamide [ 117 ]. Taken together, zonisamide may be better recommended for female epileptic patients rather than males, with close monitoring for psychiatric side effects.…”

Section: Broad and Narrow Spectrum Anti-seizure Drugsmentioning

confidence: 99%

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Akyüz

Köklü

Ozenen

et al. 2021

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: Over the decades, various interventions have been developed and utilized to treat epilepsy. However, majority of epileptic patients are often first prescribed with anti-epileptic drugs (AED), now known as anti-seizure drugs (ASD), as a first line of defense to suppress their seizures and regain their quality of life. ASDs exert their anti-convulsant effects through various mechanisms of action including regulation of ion channels, blocking of glutamate-mediated stimulating neurotransmitter interaction, and enhancing the inhibitory GABA transmission. About one third of epileptic patients are often resistant to anti-convulsant drugs, while others develop numerous side effects which may lead to treatment discontinuation and further deterioration of quality of life. Common side effects of ASDs include headache, nausea and dizziness. However, more adverse effects such as auditory and visual problems, skin problems, liver dysfunction, pancreatitis and kidney disorders may also be witnessed. Some ASDs may even result in life-threatening conditions as well as serious abnormalities, especially in patients with comorbidities and in pregnant women. Nevertheless, some clinicians had observed a reduction in the development of side effects post individualized ASD treatment. This suggest that a careful and well-informed ASD recommendation to patients may be crucial for an effective and side-effect free control of their seizures. Therefore, this review aimed to elucidate the anticonvulsant effects of ASDs as well as their side effect profile, by discussing their mechanism of action and reported adverse effects based on clinical and preclinical studies, thereby providing clinicians with a greater understanding of the safety of current ASDs.

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Section: Broad and Narrow Spectrum Anti-seizure Drugsmentioning

confidence: 99%

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Akyüz

Köklü

Ozenen

et al. 2021

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“…In addition to its antiepileptic properties, ZNS has demonstrated neuroprotective properties in experimental models of different conditions of the brain [18,19]. It also acts as an inhibitor of monoamine oxidase B (MAO-B), delays dopamine transporter reduction in Parkinson's disease, and alleviates Parkinsonian motor symptoms [20][21][22].…”

Section: Pharmacodynamicsmentioning

confidence: 99%

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

Reimers

Ljung

2019

Expert Opinion on Pharmacotherapy

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Introduction: About 70 million people worldwide are estimated to suffer from epilepsy. Despite a large variety of old and new antiepileptic drugs on the market, about 30% of people with epilepsy do not become seizure-free with medical treatment. This is a major individual and public health burden. Most of these difficult-to-treat patients are having focal seizures. Zonisamide is effective against focal seizures in adults and children and, thus, a therapeutic option for such patients. Its safety profile needs special attention. Areas covered: Herein, the authors discuss the pharmacology, clinical efficacy and the adverse effects of zonisamide. The article is derived from clinical trial data, long-term studies, meta-analyses, review articles, text books, webpages, and official license information. Expert opinion: Zonisamide has proven to be efficacious in focal epilepsy in children and adults, although it is not more effective than carbamazepine or other antiepileptic drugs. It is also effective in generalized epilepsy and in several other conditions of the CNS. Its safety profile may prevent it from becoming a first-line drug for focal epilepsy or any other indication.

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“…ZNS was reported to have antioxidant activities, including inhibiting lipid peroxidation, decreasing production of nitric oxide, and scavenging hydroxyl radicals [ 13 , 49 ]. The antioxidant properties of ZNS may contribute to the neuroprotective characteristics of this drug [ 14 ]. Therefore, the diminished nonalcoholic fatty liver disease after ZNS treatment may be related to reduced body weight and improved dyslipidemia, particularly decreased triglyceride levels, and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…It has been approved in many countries as a monotherapy or adjunctive therapy for focal or generalized onset epilepsy in adults and children [ 9 , 11 , 12 ]. In addition to the antiepileptic property, ZNS is also reported to have antioxidant activities, which may protect neurons from oxidative damage, stabilize the neuronal membranes, and prevent epileptogenic focus formation [ 13 , 14 ]. Recently, ZNS was listed as an initial monotherapy with level A efficacy/effectiveness evidence for adults with partial seizure onset by the International League Against Epilepsy [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Zonisamide Therapy Reduces Metabolic Consequences and Diminishes Nonalcoholic Fatty Liver Disease in Patients with Epilepsy

Huang

Chuang

Chen

et al. 2021

JCM

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Antiepileptic drugs that can reduce aberrant metabolism are beneficial for patients. Zonisamide (ZNS) is a chemical with antiepileptic and antioxidant activities. Here, we evaluate the efficacy of ZNS therapy on reducing obesity and decreasing risks of vascular diseases and hepatic steatosis. Clinical and metabolic indicators including body weight, body mass index (BMI), serum lipid profiles, glycated hemoglobin (HbA1c), homocysteine, and an inflammatory marker, high-sensitivity C-reactive protein (hs-CRP), were assessed at baseline and at the end of 12 and 24 weeks of treatment. Nonalcoholic fatty liver disease was evaluated using the hepatic steatosis index (HSI). A body weight reduction of ≥5% was observed in 24.6% and 32.8% of patients after 12 and 24 weeks of ZNS treatment, respectively. After adjusting for age, sex, time, and the corresponding dependent variable at baseline, the generalized estimating equation analysis revealed that the body weight, BMI, serum levels of HbA1c, triglycerides, hs-CRP, and the index for HSI were significantly declined. These results suggest that ZNS provides benefits in patients with obesity and metabolic syndrome at high vascular risk.

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A mechanistic approach to explore the neuroprotective potential of zonisamide in seizures

Cited by 13 publications

References 30 publications

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

Zonisamide Therapy Reduces Metabolic Consequences and Diminishes Nonalcoholic Fatty Liver Disease in Patients with Epilepsy

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