Discovering the pharmacodynamics of conolidine and cannabidiol using a cultured neuronal network based workflow
GDC Mendis, G Berecki, E Morrisroe, S Pachernegg, M Li, M Varney, PB Osborne, CA Reid, S Halgamuge, S Petrou
SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2019
Determining the mechanism of action (MOA) of novel or naturally occurring compounds mostly relies on assays tailored for individual target proteins. Here we explore an alternative approach based on pattern matching response profiles obtained using cultured neuronal networks. Conolidine and cannabidiol are plant-derivatives with known antinociceptive activity but unknown MOA. Application of conolidine/cannabidiol to cultured neuronal networks altered network firing in a highly reproducible manner and created similar impact on network properties suggesting engagement with a common biological target. We used principal component analysis (PCA) and multi-dimensional scaling (MDS) to compare netwo..View full abstract
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Awarded by Australian Research Council Centre of Excellence for Integrative Brain Function
The authors would like to thank Alexandra Delager and Tianran Wu for carrying out precursory experiments. We further thank Prof. Paul F. Alewood (Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia) for providing synthetic omega-conotoxin CVIE. This research was funded by the Australian Research Council Centre of Excellence for Integrative Brain Function CE14010000 awarded to S.P. and DP150103512 awarded to S.H. We would also like to acknowledge UTT Pharma for the provision of cannabidiol.