Central and Peripheral Effects of Anticholinergic Compounds

The pharmacological effects of aryl and cycloalkylaryl glycolates of piperidin, tropine and quinuclidin have been studied in relation to atropine and scopolamine. Peripheral effects (heart rate, salivation, pupil size) have been studied in dogs in relation to their behavioural effects under standardized conditions. The anticholinergic activity was further investigated on the mouse pupil and on the blood‐pressure response to acetylcholine in cats anaesthetized with pentobarbital. In dogs all the glycolates elicited behavioural effects, especially on locomotion, similar to those seen following atropine and scopolamine. Even high doses of methyl atropine produced effects indistinguishable from those produced by atropine and scopolamine. The most active compounds affected behaviour at a dose of 10 μg per kilogram body weight given subcutaneously. All compounds elicited anticholinergic activity i.e. tachycardia, mydriasis, inhibition of salivation and block of AcCh response. The most potent compounds on behaviour were quinuclidinylesters of phenyl and/or thienyl glycolic acid which also had the strongest and most prolonged classical anticholinergic effects. The results indicate that behavioural effects are related to anticholinergic activity but that other factors such as lipid‐solubility and metabolism interfere with the central activity.