Central effects of imipramine-like anti-depressants in relation to their peripheral anticholinergic activity

Summary The peripheral anticholinergic activity of imipramine, amitriptyline and their demethylated derivatives has been measured. The activity of the drugs in elevating the EEG arousal threshold in cat encephale isole preparations and in conscious cats with chronically implanted cortical electrodes has also been examined. All the drugs produced a dissociation between EEG and behavioural arousal thresholds. The pattern of the dissociation resembled that produced by hyoscine, rather than that produced by atropine, in that there was a marked sedative element in the actions of the drugs. The demethylated analogues, desmethylimipramine and nortriptyline were less potent than the parent compounds in peripheral anticholinergic activity and in elevating the EEG arousal threshold. As clinical antidepressants the demethylated analogues are no less active than the parent compounds. It is concluded that clinical antidepressant activity is not primarily associated with the anticholinergic activity of these compounds although this activity may be connected in some way with the qualitative differences between these and other types of antidepressant drugs.