chapter 4

• Cholinergic agonists are drugs that have affinity to the muscarinic and nicotinic receptors for acetylcholine
• Cholinergic agonists can also be called cholinomimetic drugs, as they mimic the actions of acetylcholine
• Acetylcholine is the ligand that binds to muscarinic and nicotinic receptors
• Acetylcholine is an endogenous neurotransmitter in the body, acting as a chemical messenger
• Sites where acetylcholine acts in the body include:

  • Preganglionic fibers terminating in the adrenal medulla
  • Autonomic ganglia (both sympathetic and parasympathetic)
  • Postganglionic fibers of the parasympathetic division
  • Muscles in the somatic nervous system
• Steps in the synthesis of acetylcholine:

  • Choline, an amino acid, is transported into nerve cells by the choline transporter with the help of sodium
  • Choline combines with acetyl coenzyme A with the help of the enzyme choline acetyltransferase (ChAT)
  • Acetylcholine is stored inside vesicles by the vesicular acetylcholine transporter (VAChT)
• Release of acetylcholine:

  • Calcium influx helps in the release of acetylcholine
  • Fusion of the cell membrane and vesicle occurs
  • Opening of gates (VAMPs and SNAPs) leads to exocytosis of acetylcholine
• Acetylcholine binds to muscarinic and nicotinic receptors post-synaptically, leading to receptor activation and a response
• Not all acetylcholine can bind to receptors
• To maintain equilibrium, the body has an enzyme called acetylcholinesterase
• Acetylcholinesterase degrades acetylcholine into choline and acetate
• Cholinergic crisis can occur due to a deficiency of acetylcholine
• Muscular contractions require acetylcholine
• Cholinergic crisis can lead to muscle paralysis
• Drugs that inhibit acetylcholine production include hemicholiniums
• Vesamicol inhibits the storage of acetylcholine
• Botulinum toxin inhibits the release of acetylcholine
• Clostridium botulinum produces botulinum toxin
• Clostridium species are spore-forming bacteria
• Botox is a cosmetic use of botulinum toxin
• Acetylcholine binds to muscarinic and nicotinic receptors
• Muscarinic receptors are named after the alkaloid muscarine
• Muscarinic receptors are metabotropic and linked to G proteins
• Nicotinic receptors can be found in ganglia and skeletal muscles
• Nicotine can act as an agonist or antagonist to nicotinic receptors
• Nicotinic receptors are divided into Nm and Nn types
• Nm receptors are found at neuromuscular junctions
• Nn receptors are found in the CNS and adrenal medulla
• Acetylcholine induces cholinergic effects or parasympathetic effects
• Cholinergic effects include actions on the parasympathetic nervous system and sweat glands
• Acetylcholine effects:

  • Excessive acetylcholine can lead to rest and digest response
  • Diaphoresis (excessive sweating)
  • Urination
  • Miosis (pupil constriction)
• Bradycardia:

  • Low heart rate (<60 beats per minute)
• Bronchoconstriction:

  • Parasympathetic effect
• Emesis:

  • Vomiting effect
• Lacrimation:

  • Production of tears
• Salivation:

  • Increased salivary production
• Sympathetic Nervous System:

  • Fight or flight response
• Parasympathetic Nervous System:

  • Rest and digest response
• Acetylcholine effects on body:

  • Dumbbells effect
  • Pupil constriction (meiosis)
  • Decreased heart rate (bradycardia)
  • Bronchoconstriction
  • Increased gastrointestinal motility and secretion
  • Urinary bladder contraction
• Acetylcholine effects on glands:

  • Stimulates sweat, salivary, and lacrimal gland production