Functional impact of the cerebral accumulation of antipsychotic drugs

• Applicants: Professor Dr. Christian Alzheimer; Professor Dr. Johannes Kornhuber; Professor Dr. Christian P. Müller, Ph.D.
• Subject Area: Biological Psychiatry
• Term: from 2014 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260234551

Antipsychotic drugs (APDs) are the mainstay in the treatment of schizophrenia. In previous studies, we found that after sub-chronic administration, APDs accumulate in synaptic vesicles, allowing them to locally build up high levels of the drug at synapses in the brain. In the previous part of the project we were also able to show that this accumulation is causally responsible for the occurrence of a therapeutic effect. While therapeutic efficacy at the beginning of APD treatment may be positively associated with dopamine D2 receptor blockade, APDs show a decreasing therapeutic efficacy in chronic treatment. The reasons for this loss of effect are not yet sufficiently understood. In this project, the role of the accumulation of APDs in the loss of efficacy in pharmacophore comparisons is to be investigated by means of new, more effective, but non-accumulating substance analogues. The planned investigations include substance synthesis, modern optical, electrophysiological, microdialytic and behavioral biological techniques.

• DFG Programme: Research Grants