The effects of the ketamine derivative N-ethyldeschloroketamine (2-oxo-PCE) on synaptic transmission and plasticity.

Abstract

Ketamine's psychotomimetic effects (e.g. hallucination, delusion) and its short acting effects have made it a popular recreational drug. Despite misuse, both classical psychoactive substances and research chemicals have shown clinical relevance in therapeutic treatments for various neurological disorders and neurogenerative diseases. Interestingly, ketamine has had worldwide clinical interest for its fast-acting antidepressant effects, which differ to conventional antidepressants that exhibit a delayed onset of action. Recently, the use of N-ethyldeschloroketamine (2-oxo-PCE), a ketamine derivative, has become a recent phenomenon in the streets. However, the effects of ‘2-oxo-PCE’ on the brain are currently unknown. Thus, the aim of the project is to characterise the pharmacology of ‘2-oxo-PCE’ by investigating its effects on N-methyl-D-aspartate receptor (NMDAR) mediated synaptic transmission and plasticity. Using in vitro electrophysiological field recordings in the CA1 region of rat hippocampal slices, the data shows that 2-oxo-PCE is a fast-acting, potent, and selective NMDAR antagonist. Therefore, the effects of 2-oxo-PCE presented here serves as a foundation on which further investigations can be build and provide the base for the development of new strategy for the treatment of depression.

Date of Award	24 Jan 2023
Original language	English
Awarding Institution	University of Bristol
Supervisor	Zuner A Bortolotto (Supervisor) & Stephen M Fitzjohn (Supervisor)