Dose responses and relationships between anticholinergic activity and mood with tricyclic antidepressants

A pilot study showed that single doses of imipramine (100 mg) produced a maximum reduction in salivation after 3 h which persisted for 72 h after drug. Effects after 3 h were reproducible in 3 subjects and differed from control levels on all 6 occasions of testing. A double-blind study in 6 subjects was then carried out to ascertain whether a dose response measured by salivary flow could be obtained for imipramine and dimethacrin, a developmental drug with fewer anticholinergic effects in animals. A further objective was to study the effects of both drugs on subjective feelings of mood, appetite, and dry mouth in order to make correlations between these effects and the anticholinergic activity. Results showed a linear log-dose response reduction in salivation for imipramine which differed significantly from placebo and dimethacrin. Significant changes on the Clyde Mood Scale in sleepiness and friendliness factors occurred only with imipramine, raising the question of whether there is a causal relationship between the central actions of imipramine and its anticholinergic activity. The significant decrease in friendliness with imipramine as compared to placebo suggests that anticholinergic activity is unlikely to be responsible for antidepressant effect, but may account for the drug's sedative action.