Cholinergic Agonists and Parasympathomimetics: Acetylcholine Biosynthesis, Receptors, Structure-Activity Relationships and Anticholinesterases

A medicinal chemistry lecture on the parasympathomimetic drugs that opens with the classification of the nervous system and the cholinergic neurotransmitter acetylcholine, then the biosynthesis of acetylcholine from L-serine through ethanolamine and choline and its storage, release and breakdown by cholinesterase. The nicotinic and muscarinic receptors and their distribution lead into the structure-activity rules of the acetylcholine skeleton - the acetyl group, the ethylene bridge and the onium group, the two-carbon chain and the alpha-methyl substitution that favours muscarinic activity. Direct and indirect agonists follow with carbachol, bethanechol, pilocarpine, physostigmine, neostigmine, edrophonium and echothiophate, their uses in glaucoma, myasthenia gravis and Alzheimer's disease, and the cholinesterase reactivator pralidoxime as the organophosphate antidote.