MUSCARINIC M(1)-RECEPTOR AGONISTS - POTENTIAL IN THE TREATMENT OF ALZHEIMERS-DISEASE

Extensive degeneration of cholinergic neurons occurs early in Alzheimer's disease and correlates with the loss of cognitive function, Cholinergic replacement therapies attempt to compensate for neuronal loss by increasing endogenously released acetylcholine or directly stimulating cholinergic receptors. Recently, new drugs have been developed that are specific agonists of postsynaptic muscarinic M(1) acetylcholine receptors, Unlike acetylcholinesterase inhibitors, these M(1)-receptor agonists do not rely on remaining presynaptic neurons for their effect or stimulate the inhibitory presynaptic M(2) autoreceptors. Preliminary clinical evidence suggests that some of these compounds may display measurable cognitive and behavioural effects. A clear assessment of the value of M(1)-agonists depends on the proper determination of the dosages that can be well tolerated by patients in clinical efficacy trials.