Muscarinic agonists for senile dementia: past experience and future trends

Clinical experience with muscarinic agonists in the symptomatic treatment of Alzheimer's disease includes studies of the effects of pilocarpine, arecoline, bethanechol, oxotremorine and RS 86. Although the results are somewhat conflicting, there is evidence that a subgroup of patients may respond with an improvement of cognitive and/or behavioural function. The existing agents tend to induce adverse effects due to the stimulation of peripheral muscarinic receptors. Furthermore they reduce (at least in vitro) acetylcholine release by an action on presynaptic receptors. Strategies to overcome these problems include the development of potent agonists with high blood-brain barrier penetration, the search for agents selective for muscarinic receptor subtypes (using cloned receptors as tools) and the identification of agents acting as presynaptic receptor antagonists, to increase acetylcholine release.