XQ Deng
Jinggangshan University, China
Title: H3R receptor antagonist in the discovery of antiseizure compounds
Biography
Biography: XQ Deng
Abstract
Statement of the Problem: Epilepsy is the second most common neurological disease after cerebrovascular disease. Chronic and recurrent epilepsy not only cause physical damage such as memory loss and emotional expression disorder, but also reduce the quality of daily life of patients, increasing their psychological burden, and leading to a high proportion of accidental deaths. The third generation of antiseizure drugs (ASDs) represented by Eslicarbazepina and Brivaracetam showed better antiseizure effect, pharmacokinetics and safety. However, these drugs have not reduced the proportion of refractory epilepsy or exhibited trauma repair.
Methodology & Theoretical Orientation: With the application of target-based design in antiepileptic drug discovery, an increasing number of target-based antiepileptic active molecules have been discovered. The histamine H3 receptor is a promising new target for antiepileptic treatment. The use of the histamine H3 receptor as a target for epilepsy treatment has been confirmed since 2001. Unfortunately, pharmacologists have not paid too much attention to it, and no antiseizure drug based on the histamine H3 receptor was approved. This study is aim to discover new antiseizure drugs based on histamine H3 receptor(H3R).
Findings: The H3R antagonist provided protection in MES-induced seizure model. What is more, H3R antagonist repaired the damaged hippocampal neurons. Some antiseizure molecules has been identified from a large number of H3R antagonists, and the antiseizure activity was positively related to their H3R inhibitory on the premise of ensuring a certain lipid water Partition coefficient. And their antiepileptic activity can be reversed by H3R agonist RAMH.
Conclusion & Significance: H3R is a potent target for the treatment of epilepsy. H3R antagonist not only inhibit the seizure, but also repair the damaged hippocampal neurons coused by epilepsy. Discovery of new antiseizure drugs among H3R antagonistss is practicable and encouraging.