Differences in the Agonist Binding Properties of Muscarinic Receptor Subpopulations in the Rat Cerebral Cortex and Myocardium

Abstract

Low levels of presynaptic cholinergic markers such as choline acetyltransferase seem to be a characteristic feature of certain brain regions of people with senile dementia of the Alzheimer type (see eg. Bartus et al., 1982; Coyle et al., 1983 for reviews). In contrast, there seems to be little if any change in the density of muscarinic receptors located on the target cells of the cholinergic neurones (10 references cited in Bartus et al., 1982). As the muscarinic cholinergic system is thought to be involved in the storage and retrieval of newly acquired information it has been considered that a muscarinic agonist might be used therapeutically to compensate for the “cholinergic deficit” in senile dementia of the Alzheimer’s type and alleviate some of the memory problems associated with the disease. Very recently, the muscarinic agonist RS 86 has been shown to improve general cognitive functions in a minority of Alzheimer’s patients (Wettstein and Spiegel, 1984). In general however, the doses of muscarinic agonists which can be used for this purpose are limited by additional effects produced by their actions on muscarinic receptors in other tissues. What is required is an agonist which will selectively stimulate specific muscarinic functions in the cerebral cortex.