Antiseizure medication discovery: Recent and future paradigm shifts

Talevi, Alan

doi:10.1002/epi4.12581

Cited by 13 publications

(7 citation statements)

References 62 publications

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“…Padsenovil's mechanism of action is not fully elucidated, but it is known that it does not bind directly to the GABA receptors. However, it exhibits an antiepileptic action [126]. Trials involving this new drug were conducted, i.e., NCT02495844 and NCT03373383, which involved 55 and 411 participants, respectively.…”

Section: Padsenovilmentioning

confidence: 99%

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

Boleti,

Cardoso,

Frihling

et al. 2024

Brain Sciences

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Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the initial unsatisfactory effects of medications, are important considerations. Although there are several third-generation antiepileptic drugs currently available, their multiple side effects can negatively affect patient quality of life. The inheritance and etiology of epilepsy are complex, involving multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play crucial roles in maintaining the normal physiology of different neurons. Dysregulations in neurotransmission, due to abnormal transmitter levels or changes in their receptors, can result in seizures. In this review, we address the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Furthermore, we extensively explore the neurological mechanisms involved in the development and progression of epilepsy, along with its risk factors. Furthermore, we highlight the new therapeutic targets, along with pharmacological and non-pharmacological strategies currently employed in the treatment of epileptic syndromes, including drug interventions employed in clinical trials related to epilepsy.

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Section: Padsenovilmentioning

confidence: 99%

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

Boleti,

Cardoso,

Frihling

et al. 2024

Brain Sciences

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“…When the synaptic transmission function is abnormal, the equilibrium between excitation and inhibition of the neural network is destroyed, which induces abnormal firing of neurons and finally leads to seizures [186]. Despite more than 40 kinds of antiseizure drugs have been used in clinic in recent years, about onethird of patients are still unable to effectively control epileptic seizures [187].…”

Section: Epilepsy Overviewmentioning

confidence: 99%

Targeting AKAP79/150 in Human Disorders: An Emerging Opportunity for Future Therapies?

Chen,

Chu,

et al. 2023

PNEURO

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A-kinase anchoring protein 79/150 (AKAP79/150) is an important scaffolding protein, which anchors various important proteins to locate in appropriate synaptic domains to regulate excitatory synaptic intensity. With sweeping advances in the biology of AKAP79/150 and its critical role in the pathophysiology of various human disorders, more and more evidence is breeding new opportunities for potential therapeutic intervention in an attempt to improve the clinical outcomes of those patients. Herein, we review the basic structure and main functions of AKAP79/150, focusing on the pathophysiological mechanisms of AKAP79/150 in different human disorders, with a particular emphasis on the inflammatory pain, epilepsy, and depression, to discuss their potential therapeutic intervention value in patients with those diseases.

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“…Epilepsy treatments are categorized into pharmacological and non-pharmacological approaches, such as surgery and nerve stimulation [ 10 ]. Despite the availability of more than 30 FDA-approved anti-seizure medications, one third of patients do not achieve adequate seizure control [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Novel Anti-Seizure Potential of Validamycin A Using Zebrafish Epilepsy Model

Lee,

Banik,

Lee

et al. 2024

Molecules

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Epilepsy is a prevalent neurological disorder characterized by recurrent seizures. Validamycin A (VA) is an antibiotic fungicide that inhibits trehalase activity and is widely used for crop protection in agriculture. In this study, we identified a novel function of VA as a potential anti-seizure medication in a zebrafish epilepsy model. Electroencephalogram (EEG) analysis demonstrated that VA reduced pentylenetetrazol (PTZ)-induced seizures in the brains of larval and adult zebrafish. Moreover, VA reduced PTZ-induced irregular movement in a behavioral assessment of adult zebrafish. The developmental toxicity test showed no observable anatomical alteration when the zebrafish larvae were treated with VA up to 10 µM within the effective range. The median lethal dose of VA in adult zebrafish was > 14,000 mg/kg. These results imply that VA does not demonstrate observable toxicity in zebrafish at concentrations effective for generating anti-seizure activity in the EEG and alleviating abnormal behavior in the PTZ-induced epileptic model. Furthermore, the effectiveness of VA was comparable to that of valproic acid. These results indicate that VA may have a potentially safer anti-seizure profile than valproic acid, thus offering promising prospects for its application in agriculture and medicine.

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Antiseizure medication discovery: Recent and future paradigm shifts

Cited by 13 publications

References 62 publications

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

Pathophysiology to Risk Factor and Therapeutics to Treatment Strategies on Epilepsy

Targeting AKAP79/150 in Human Disorders: An Emerging Opportunity for Future Therapies?

Assessment of the Novel Anti-Seizure Potential of Validamycin A Using Zebrafish Epilepsy Model

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