How can preclinical cognitive research further neuropsychiatric drug discovery? Chances and challenges

Disorders of the brain pose the biggest health challenge of this century with new and highly efficacious medications urgently needed. This article discusses the challenges of meeting this increasing demand by neuropsychiatric drug discovery.

The current psychopharmacological armamentarium relies on targets discovered several decades ago. Moreover, a major part of the current pipeline of potential cognitive enhancers also contains compounds with multiple failed modes of action which had not been properly validated before the clinic. Further, the feasibility limits of preventive pharmacology should also be taken into account. Advancements in neuroimaging and genetic studies have highlighted epigenetic regulation and synaptic plasticity as potential 'hot points' for pharmacological interventions in neuropsychiatric disorders. However, in the meantime new, rapidly evolving technologies have given rise to alternative treatment options such as brain stimulation, cell and gene therapy.

Neuropsychiatric drug discovery should turn toward non-neurotransmitter-related targets such as actors of epigenetics and synaptic plasticity to give chance to produce more efficacious treatments and retain its competitiveness against the new high-tech medications like neuroprosthetics, gene, and cell therapy. To increase the success rate in the clinic, the potential targets raised by basic research should be validated in preclinical animal models before launching industrial drug development projects.