Non-selectivity of amitriptyline for subtypes of brain muscarinic receptors demonstrated in binding and functional assays
European Journal of Pharmacology
Antidepressants; Brain cells; cAMP; Muscarinic acetylcholine receptor subtypes; Phosphoinositides; Pirenzepine
The characteristics of interaction of amitriptyline, a tricyclic antidepressant, with rat brain muscarinic receptors were assessed using both radioligand binding and functional assays. In competition studies, amitriptyline displaced muscarinic ligand binding from a single high-affinity site in homogenates of various brain regions which have a different distribution of M1 and M2 receptor subtypes. The affinity of amitriptyline for muscarinic receptors was also comparable in all brain regions. Furthermore, amitriptyline indentified a single species of muscarinic receptors in intact cells dissociated from the cerebral cortex and in cerebrocortical slices. The non-selectivity of amitriptyline for muscarinic receptor sybtypes in these preparations was in contrast to the selectivity exhibited by pirenzepine. This non-selective nature of amitriptyline was also evident in functional assays, since this antidepressant was equipotent at antagonizing M1-mediated increase in phosphoinositide hydrolysis and M2-mediated inhibition of cyclic AMP formation in dissociated cortical cells. Atropine was also equipotent at blocking both responses but was 20- to 30-fold more potent than amitriptyline. These results demonstrate that amitriptyline behaves as a non-selective muscarinic antagonist using both radioligand binding and functional measurements. © 1988.
McKinney, M., Lee, N., Anderson, D., Vella-Rountree, L., & El-Fakahany, E. (1988). Non-selectivity of amitriptyline for subtypes of brain muscarinic receptors demonstrated in binding and functional assays. European Journal of Pharmacology, 157 (1). http://dx.doi.org/10.1016/0014-2999(88)90470-0