KEY EXPERTISES IN THE GROUP

- Organic chemistry: Multistep synthesis of complex small molecules
- Organic chemistry: Discovery of new methodology
- Rational Ligand Design
- Structure-activity-relationship studies
- Computational chemistry / molecular modeling
- Advanced medicinal chemistry

 
OUR RESEARCH INTERESTS

In the Chemical Neuroscience Group we focus on the discovery of novel ligands targeting the central nervous system (CNS) and the development of new methodology for their efficient synthesis.

To achieve our ambitious research objectives, we take advantage of state-of-the-art methodology within the core disciplines organic chemistry, medicinal chemistry, and computational chemistry.

Once a new ligand has been designed and synthesized it will be used to study the function of the healthy as well as the diseased brain. We are engaged in both in vitro and in vivo (animal) studies in close collaboration with pharmacologists and biologists.

Examples of synthesized ligands are DCAN, BOAD, 3CPP, 2PPA and recently UCPH-101* which is the first selective inhibitor of EAAT1:

*Commercially available from Hugin NeuroChemicals. 

GLUTAMATE IN THE CNS: BACKGROUND

In the mammalian central nervous system, (S)-glutamate (Glu) functions as the major excitatory neurotransmitter. Once released from the pre-synaptic neuron into the synaptic cleft, Glu activates a number of pre- and post synaptic ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs, respectively). Uptake of Glu from the synaptic cleft is carried out by the action of the Excitatory Amino Acid Transporters (EAATs) - also referred to as glutamate transporters (GluT).

In the healthy CNS, activation of Glu receptors is involved in important neuro-physiological processes such as memory and learning, motor functions, and neural plasticity and development. However, under conditions of metabolic stress and oxygen depravation Glu is a neurotoxic agent. Thus, it is believed that diseases such as anxiety disorders, schizophrenia, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS) and epilepsy may be directly related to disordered glutamatergic neurotransmission originating from dysfunction of either the Glu receptors (iGluR or mGluR) or the Glu transporter system (EAATs).