Drugs Affecting the Cholinergic System

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.