Off-campus University of Richmond users: To download campus access theses, please use the following link to log in to our proxy server with your university username and password.

Date of Award

2026

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Colleen Carpenter-Swanson

Abstract

Epilepsy is a chronic neurological disease that is characterized by unprovoked, recurrent seizures. A seizure is abnormal electrical activity of the brain that may lead to uncontrolled jerky movements, loss of consciousness, and ultimately death. There are ~50 million people living with epilepsy globally and roughly 30% of them do not respond to available antiepileptic drugs. This thesis examines the antiepileptic potential of phenylcyclohexenones (PCHs), a novel class of sodium channel modulators developed by OB Pharmaceuticals. The substituted-PCH family of compounds holds promise in addressing this unmet need for innovative seizure management options. Two candidates, TD561 and TD562, have been efficacious in reducing seizure activity in focal models of epilepsy: the rat amygdala kindling and the mouse 32‐mA 6‐Hz model. Here, we aim to further assess the safety and antiseizure efficacy of these and related PCHs (TD567, TD597) in the zebrafish animal model. These organisms serve as a model of generalized epilepsy with translational potential because of their high degree of genetic similarity with humans.

To test drug efficacy, larvae were exposed to various concentrations of the PCHs and behavior (total distance travelled) was quantified before and after seizure induction with pentylenetetrazole (PTZ), a GABAA receptor antagonist. We utilized a 96-well format and automated locomotion detection using DanioVision system running EthoVision software (DanioVision, Noldus Information Technology) and statistical analyses were performed with GraphPad Prism 10. Toxicity was also evaluated by monitoring heart rate and touch responses after each experiment. We found that TD561, TD562 and TD597 dose-dependently reduced seizure-like activity and did not alter basal movement and showed no observable toxic effects at almost all concentrations. TD567 also showed no evidence of toxicity but failed to demonstrate efficacy in our animal model. Collectively, these findings position PCHs as a compelling and translationally relevant class of candidates for next-generation antiepileptic drug development.

Download

Available for download on Saturday, May 17, 2031

Share

COinS