PhD defence G. (Gunnar) Flik

The histaminergic system and its interaction with relevant central neurotransmitter systems

The current thesis shows that the histaminergic H3 receptor is an interesting target for multiple brain disorders. Several Histamine 3 antagonists have already been tested in the clinical phase after demonstrating preclinical pharmacological effects in a number of indications such as cognitive effects in neurodegeneration. However, the question remains why there is no clear pharmacological effect demonstrated in the clinic. Difference between animal and human in the isoforms of the H3 receptor may be one reason. The existence of H3 receptor isoforms appears to be consistent with the pharmacological heterogeneity of the H3 receptor.Another reason could be the effect of overstimulation of the histaminergic system. We may therefore miss the real value of the histaminergic system. The histaminergic system fine-tunes other neurotransmitter mechanisms in the brain. This can cause an imbalance of several mechanisms. In brain disorders, the balance between multiple neurotransmitter mechanisms seems to be lost. Therefore, in this thesis, complementary therapies were suggested to existing therapies in Parkinson's disease and schizophrenia. Add-on therapies appear to be a promising approach to increasing cognitive function and reducing negative symptoms.This thesis aims to provide a better understanding of the communication between the different neurotransmitter systems and the histaminergic system. It could shed light on designing necessary follow-up studies to reveal how we can use the histaminergic system to cure or slow down diseases such as Alzheimer's, Parkinson's and psychiatric disorders.

Promotores Prof.dr. T.I.F.H. Cremers