Cholinergic System

What enzyme is needed for ACh biosynthesis from Acetyl-CoA and Choline

Choline Acetyltransferase

What enzyme is needed for ACh metabolism from Acetate and Choline

Acetylcholinesterase (AChE)

Which is a drug target Choline Acetyltransferase or Acetylcholinesterase

AChE

Where are muscarinic receptors located

• Brain

• Effector organs innervated by parasympathetic neurons

• Postganglionic sympathetic release ACh

  • Except in sweat glands under sympathetic control

M1 and M3 signaling pathway

• Coupled to Gq, which stimulates PLC

  • PIP2 hydrolyzed into IP3 and DAG

M2 signaling pathway

• Coupled to Gi

  • Inhibits adenylyl cyclase to decrease cAMP

Muscarinic physiological functions

Salivary gland and GI organs (M3)

• Salivation

• gastric acid secretion

• increase tone and motility of GI smooth msucle

bladder contraction

lacrimation

sweating (SYMPATHETIC)

Muscarinic agonist drugs

Pilocarbine

Cevimeline

Muscarinic agonist uses

Xerostomia

Sjorgren’s syndrome

Dry mouth

Muscarinic agonist C/I

Asthma

Muscarinic agonist properties

increase glandular secretion of

• Saliva

• Sweat

• Tears

Increase smooth muscle tone in

• GI

• Bladder

• Bronchi

Muscarinic antagonists agents

Atropine

Hyosycamine
Dicyclomine

T/F: Hyosycamine is the I-Isomer of Atropine responsible for most biological activity

True

Muscarinic antagonists typical indication

antispasmodic

Muscarinic antagonists effect

• Tachycardia

  • more likely in atropine

• decrease tone and motility in GI

• prolonged gastric emptying and intestinal transit tiem

• inhibtion of gastric secretion

Muscarinic antagonists ADR

Dry mouth

Blurred vision

Constipation

Urinary retention

Muscarinic antagonists C/I

Glaucoma due to blockage of drainage of aqueous humor block