Abstract
Epilepsy is a chronic neurological disorder affecting nearly 65-70 million people worldwide. Despite the observed advances in the development of new antiepileptic drugs (AEDs), still about 30-40% of patients cannot achieve a satisfactory seizure control. In our current research, we aimed at using the combined results of radioligand binding experiments, PAMPA-BBB assay and animal experimentations in order to design a group of compounds that exhibit broad spectrum of anticonvulsant activity. The synthesized 4-alkyl-5-substituted-1,2,4-triazole-3-thione derivatives were primarily screened in the maximal electroshock-induced seizure (MES) test in mice. Next, the most promising compounds (17, 22) were investigated in 6 Hz (32 mA) psychomotor seizure model. Protective effect of compound 22 was almost similar to that of levetiracetam. Moreover, these compounds did not induce genotoxic and hemolytic changes in human cells as well as they were characterized by low cellular toxicity. Taking into account the structural requirements for good anticonvulsant activity of 4-alkyl-5-aryl-1,2,4-triazole-3-thiones, it is visible that small electron-withdrawing substituents attached to phenyl ring have beneficial effects both on affinity towards VGSCs and protective activity in the animal models of epilepsy.
Highlights
Epilepsy is a chronic neurological disorder affecting nearly 65–70 million people worldwide [1]
We have identified 4-alkyl-5-aryl-1,2,4-triazole-3-thiones as a promising group of antiepileptic drug candidates [4,5,6,7]
We believe that the results presented in this manuscript will provide valuable insights on the design and development of new antiepileptic drugs (AEDs) candidates
Summary
Epilepsy is a chronic neurological disorder affecting nearly 65–70 million people worldwide [1]. Epileptics suffer from the disease’s symptoms, but they are at an increased risk of death [2]. Treatment of epilepsy is based mainly on the properly selected pharmacotherapy. Despite the observed advances in the development of new antiepileptic drugs (AEDs), still about 30–40% of patients cannot achieve a satisfactory seizure control [3]. New AEDs usually have milder side-effects, better pharmacokinetic profile and slightly improved efficiency. These drugs have not significantly improved the outcome of treatment in patients with therapyresistant epilepsy. There is an immense need for new AEDs exhibiting efficiency against a broad spectrum of seizures
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
