Neuromapping techniques in drug discovery: pharmacological MRI for the assessment of novel antipsychotics

Treatment of psychiatric and neurological diseases represents a substantial unmet medical need, but the development of novel, effective and safe drugs is proving difficult. While substantial improvement over existing pharmacological agents is expected from new molecular targets emerging in the genomic era, the validation and exploitation of novel mechanisms of action is a lengthy and costly process. The use of neuroimaging techniques, and more specifically of functional and pharmacological magnetic resonance imaging (MRI), has been advocated as a powerful approach to this problem, providing translational biomarkers for the objective assessment of drug activity on brain function, and possibly surrogate markers of clinical response.

The authors review the recent application of functional and pharmacological MRI (phMRI) in the study of novel treatments of psychosis based on glutamatergic mechanisms. Furthermore, they review contribution of functional imaging in the target validation and early assessment of drugs exploiting glutamatergic mechanisms as an example of potentially impactful exploitation of neuroimaging methods in drug discovery.

While functional neuroimaging methods may provide useful markers of drug activity and response to treatment, their translational potential, that is, their use to bridge animal and human investigations is seldom exploited. The application of phMRI in the study of novel antipsychotics based on glutamatergic mechanisms represents an example of functional neuroimaging as a powerful means to link preclinical and clinical research, thus providing a paradigm that may help expedite progression into the clinical phase of novel mechanisms for the treatment of psychiatric and neurological diseases.