TRPC4/5 inhibitors: Phase I results and proof of concept studies.

Transient receptor potential canonical (TRPC) ion channels are expressed in areas of the brain responsible for processing emotion and mood and have been implicated in the pathophysiology of internalizing disorders such as major depressive disorder and anxiety disorders. This review outlines the rationale for targeting TRPC ion channels for drug development, with specific focus on TRPC4 and TRPC5. We provide preclinical evidence that the lack of TRPC4 and TRPC5 channels or its pharmacological inhibition attenuate fear and anxiety without impairing other behaviors in mice.

Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex.

Neuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine's antidepressant (AD) mechanisms of action. However, due to different methodological approaches, different investigated populations, and varying measurement timepoints, results are not consistent, and the functional significance of the observed brain changes remains a matter of open debate. Inhibition of glutamate release during acute ketamine administration by lamotrigine provides the opportunity to gain additional insight into the functional significance of ketamine-induced brain changes.

The development process of 'fit-for-purpose' imaging biomarkers to characterize the tumor microenvironment.

Immune-based treatment approaches are successfully used for the treatment of patients with cancer. While such therapies can be highly effective, many patients fail to benefit. To provide optimal therapy choices and to predict treatment responses, reliable biomarkers for the assessment of immune features in patients with cancer are of significant importance.