Within the FASC-unit, the research group "Experimental Neuropharmacology" is involved in in vivo neurochemistry, neuropharmacology and pharmacokinetics in animal models of a number of neurological disorders. The group is particularly interested in Parkinson's disease, epilepsy, focal transient brain ischemia and more recently cognitive decline and depression. The aim is to study the pathophysiological changes in the brain at different levels in order to define new strategies for drug development and drug testing.
In vivo microdialysis is used to sample different neurotransmitters such as dopamine, serotonin, acetylcholine, glutamate and gamma-aminobutyric acid (GABA) from specific brain areas in freely moving rodents. The neurochemical data thus obtained are supported by behavioural tests (rotational behaviour in parkinsonian rats, morris water maze, evaluation of seizure severity, ... and immunological techniques such as immunocytochemistry and western blotting (tyrosine hydroxilase, caspases, NOS, glutamate and GABA transporters, ...).
The group has a strong analytical background and is specialized in developing and validating microbore LC techniques with electrochemical or fluorescent detection for the determination of neurotransmitters in microdialysates. It also has ample experience with the capillary electrophoresis technique. More recently, capillary / nano LC-MS/MS was introduced to determine neuropeptides and drugs in microdialysates. For some of these drugs such as anti-epileptics, the microdialysis technique is also applied to study their pharmacokinetics and brain distribution with the ultimate goal to carry out PK-PD modeling.
Solutions to deal with key bottlenecks in the pharmaceutical R&D process, offered by FASC, consist of:
- screening of new compounds in different animal models for neurological diseases
- evaluation of existing compounds
- unraveling pathophysiological processes
- unraveling new potential mechanisms of action, drug targets
- predicting and modulation of blood-brain-barrier passage and active efflux systems
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- determination of disease-related biomarkers: neurotransmitters, neuropeptides, etc
- mechanism-based pharmacokinetic and pharmacodynamic modeling using neurotransmitters as biomarkers for predicting drug effects in the brain and drug efficacy based on drug plasma concentrations