Evaluation of potential radioligands for muscarine receptor subtypes
06 / 2000 - unknown
An important neuropathological feature in Alzheimer's disease (AD) is the degeneration of cholinergic neurons. Neurons equipped with the M2-receptor subtype on the presynaptic membrane are thought to be among the first to degenerate in AD. In vivo quantification of these M2-receptors might therefore eventually be of clinical relevance in the (differential) diagnostic process of AD and may play an even more important role in monitoring either progression of the disease or the effects of drugs, whether or not in an experimental setting. This kind of quantification can be achieved by using imaging techniques like PET or SPECT, using a radioligand with high selectivity for the M2-receptor subtype. Unfortunately, none of the ligands synthesised to date has proven to be highly selective for the M2-receptor subtype while most of them also bind to the M1 and M3-5 subtypes.
The goal of this substudy is to investigate the binding properties of 8 newly synthesised (unlabeled) radioligands to muscarinic receptors. Data is obtained from displacement studies with [3H]-N-methyl scopolamine and membranes from CHO cells transfected with human recombinant muscarinic receptors. Then, selectivity for the M2-receptor subtype of the ligands is estimated. The most selective potential ligand will be subject of biodistribution and subsequent blocking experiments in the near future.