The United States National Institutes of Health provides support to ELKH researchers working on developing the tools needed to visualize the nanoscale distribution of D3 dopamine receptors

Within the framework of the PharmacoSTORM procedure developed by IEM and TTK researchers ‒ with the help of designed fluorescent molecules and the use of STORM (Stochastic Optical Reconstruction Microscopy) super-resolution microscopy ‒ it is possible to perform pharmacological measurements on receptors, ion channels, and enzymes with nanometer precision. István Katona and Miklós György Keserű have recently begun to investigate the functioning of the Hungarian-developed cariprazine with the help of this technology. Their initial results were published in the journal Nature Communications in 2021.

Cariprazine is one of the most promising new drugs in the treatment of schizophrenia, bipolar disorders, and depression, and the study of its mechanism of action may open new avenues in the field of research into the neurobiological basis of psychiatric illnesses. The broad therapeutic profile of cariprazine, its strong affinity and preference for D3 dopamine receptors, as well as the brain distribution pattern of these receptors, suggest that several different types of nerve cells must be investigated in order to fully understand its complex mechanism of action. At the same time, these cells produce very few D3 receptors, which is why the supported project involves the development of more effective markers and test methods that provide higher optical and spatial resolution.

D3 dopamine receptors may play a role in the regulation of pathological impulse transmission processes, in the communication between cells and synapses of the nervous system, and in the brain processes of reward and learning. By visualizing the nanoscale distribution of D3 receptors and developing new tools for studying molecular changes associated with pathological processes, research can also provide insight into the neurobiological mechanisms underlying the co-occurrence of substance use and bipolar disorders.

About the NIH R21 grant:

The R21 grant mechanism aims to encourage exploratory research by providing support for the early and conceptual stages of project development. The supported projects are expected to either open new paths going forward or develop previous discoveries in new directions and find new applications for them. High-risk and high-added-value research can lead to breakthroughs in a given field, or result in new techniques, agents, methods, models, or applications that will impact biomedical, behavioral, or clinical research.