Tricyclic antidepressants as antimuscarinic drugs: In vivo and in vitro studies

The antagonistic activity of nortriptyline, amitriptyline and imipramine to the hypothermic and tremorgenic activity of oxotremorine was determined in mice. The peripheral anticholinergic relative potencies of these drugs were evaluated by following the dose-dependent time profiles of their mydriatic activity. The binding constants of the antidepressant agent toward the central muscarinic receptor from the mouse whole brain homogenate were determined in vitro, and could be correlated with the ed₅₀ values found for the three drugs' in vivo responses. The three antidepressants tested were found to be 100-fold less active than scopolamine. HBr in all four biological preparations selected. Their anticholinesterase activity towards the enzyme in whole mouse brain homogenate was found to be too low to make any possible contribution to their activity in vivo. The relationships between structure and function and the possible contribution of their antimuscarinic property to the observed in vivo effects are discussed.