Although general anaesthetics (GA) have been in use since 1846 and hundreds of millions of people every year worldwide undergo surgery, we still lack a full explanation of the mechanism of action of most agents used in general anaesthesia. This knowledge gap has hindered our capacity to address some aspects of general anaesthesia that remain problematic, in particular recovery from deep anaesthesia, especially in elderly patients. Considering the shift to older demographics and the increased reliance on general anaesthesia for most surgeries, there is a clear need to better understand why recovery can sometimes be difficult or unduly prolonged, and whether designer drugs can help with this process. This lack of a capacity to counteract the anaesthesia process has serious secondary consequences, such as increased length of hospital stay, and more post-operative complications, including post-operative cognitive decline.
The aim of this study is to investigate whether two propofol analogues are effective in reversing the effects of propofol on syntaxin1A mobility at the synapse when provisioned in combination with clinically relevant concentrations of propofol. This work will be done in fly brains and mammalian cell cultures in the laboratory of Professor Bruno van Swinderen at the Queensland Brain Institute.
The study will provide a platform for screening and testing candidate reversal agents for general anaesthesia, based on our growing understanding of a relevant presynaptic process that is targeted alongside the better-understood post-synaptic receptor targets. This platform will help establish novel approaches to reversing GA, based on a better understanding of the underlying molecular processes.
Professor Andre van Zundert, Royal Brisbane and Women’s Hospital, Queensland.
Associate Investigator: Professor Bruno van Swinderen, Queensland Brain Institute.
The project was awarded $A69,687 through the ANZCA research grants program for 2023.