[The virtual synapse what is its contribution to understanding cholinergic neural transmission?]

Since the launch of cholinomimetics on the Alzheimer market, large clinical trials have been performed with the aim of linking clinical scales to the pathology and pharmacology of the cholinergic neurotransmission system. However, given the additional mode of action of nicotinic receptor modulation in the case of galantamine, and of butyrylcholinesterase inhibition in the case of rivastigmine, it is of interest to study the link between this additional pharmacology and the specific clinical outcomes. This may be helpful in identifying new targets and optimising the clinical development of new compounds. One of the most appropriate and promising approaches is to use mathematical modelling to describe the complex pharmacology of these agents and their relationships with clinical outcomes. The virtual synapse is based upon the full integration of neuroanatomical and neuropharmacological datasets, to which complete pharmacological information on the drugs is added. Validation of this system is performed by predicting the outcome in a preclinical setting and subsequent testing of this hypothesis. Some examples of this model with regard to the prediction of clinical outcome are presented.