This chapter is a comprehensive account of the medicinal chemistry of drugs
affecting the cholinergic system. It provides the mechanism of drug action and the
structure-activity relationship (SAR) of the cholinergic and related drugs. After a study
of this chapter, students will be able to:
• Relate principles of acetylcholine (ACh) discovery, biosynthesis, storage, transport,
and metabolism.
• Describe the effects of agonism and antagonism of cholinergic receptors and
modulation of ACh levels at the synapse.
• Describe cholinergic biochemistry and neurochemical interactions.
• Compare muscarinic and nicotinic receptor subtypes.
• Illustrate the mechanism of action, structure-activity relationship (SAR), metabolites,
and clinical considerations of:
▪ muscarinic receptor agonists
▪ muscarinic receptor antagonists (anticholinergics)
▪ acetylcholinesterase (AChE) inhibitors
o reversible
o quasi-irreversible
o antidotes for irreversible inhibitors
▪ neuromuscular blocking agents
Keywords: Acetylcholine, Acetylcholinesterase inhibitors, Anticholinergics,
Alzheimer`s Disease, Muscarinic agonists, Neuromuscular Blocking Agents,
Structure-activity relationship.
