Design, Synthesis, Anticonvulsant Evaluation, and Molecular Docking Studies of New GABA_A Agonist Derivatives

Abstract

Background: The side effects and drug resistance associated with current antiepileptic drugs necessitate the design and synthesis of new candidate anticonvulsant agents. Objectives: The present study aimed to design, synthesize, and screen a new series of gamma-aminobutyric acid (GABA) agonist derivatives for the treatment of seizures in an animal model. Methods: The test chemical compounds were synthesized using known synthetic routes, and their structures were confirmed by various spectroscopic methods. Anticonvulsant activity was evaluated using the pentylenetetrazole (PTZ) animal model. Molecular docking studies were conducted to assess interactions with the GABAA receptor. Results: Some synthesized compounds significantly improved seizure symptoms and reduced mortality rates in the PTZ model. Derivative 3c demonstrated a correlation with the GABAA receptor in the flumazenil test. Conclusions: The synthesized molecules exhibited moderate to good activity compared to the control group. Derivative 3c notably increased seizure latency relative to the control. Flumazenil inhibitory effect tests indicated that 3c protects against PTZ-induced seizures via the synaptic GABAA receptor.