Abstract
Dimethylaminoethanol (DMAE) and dimethylaminopropanol (DMAP) possess indirect cholinomimetic activity in the isolated guinea pig ileum preparation. This activity does not involve the stimulation of nicotinic receptors. Their ability to release acetylcholine was indicated by lack of stimulant activity in tissues pretreated with morphine or tetrodotoxin and in cooled tissues, and was confirmed by assay of released acetylcholine. The closely related cholinomimetic compounds choline and dimethylaminoethane (DME) acted predominantly through muscarinic and nicotinic receptor stimulation respectively. Isoamylalcohol was devoid of stimulant activity. Indirect cholinomimetic activity appears to be dependent on the presence of a tertiary nitrogen group (as in DMAE, DMAP and DME). The absence of an hydroxyl group results in direct stimulation of nicotinic receptors (DME) while in the presence of an hydroxyl group (DMAE, DMAP), acetylcholine release is ‘aganglionic’. Quaternisation of the nitrogen (choline) results in direct stimulant actions on post-junctional cholinergic receptor sites.
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