F1000 Research has published an article entitled “In search of the mechanisms of ketamine’s antidepressant effects: How robust is the evidence behind the mTor activation hypothesis” co-authored by PAASP’s managing partner Anton Bespalov, together with colleagues from AbbVie, Servier, Pfizer and Alkermes.
Independently of each other, all four groups followed the reports that the antidepressant-like action of ketamine is mediated by the activation of mTOR-dependent intracellular signaling cascades. These studies were motivated by the need to identify cellular mechanisms underlying antidepressant effects of ketamine that would enable development of novel drugs with similar rapid and long-lasting effects of intravenous ketamine, but which are free from ketamine’s side-effects.
However, and despite considerable efforts, these independent teams could not confirm robust effects of ketamine on markers reported to be affected in the original publication by Li et al. (2010). Thus, detection of the effects of ketamine on mTOR seems to require special conditions that are difficult to identify and establish without detailed information regarding specific methods and materials and the execution of individual experiments. In the absence of this knowledge, the effects of ketamine appear not to be robust enough for drug companies to build their drug discovery programs on.
This paper is an example of a successful information sharing that may be important to identify research findings that are robust and those that, while scientifically important and correct, may not be robust for the purposes of drug R&D. To facilitate this information sharing, the ECNP Preclinical Data Forum Network is developing a mechanism that provides a communication and technological platform for preclinical research with the important aim of sharing experiences based on specific research projects and experiments.