Acetylcholine Pharmacology Quiz and Structure Review

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Questions and Answers

Why can't acetylcholine be administered orally?

It has a high affinity for butyrylcholinesterase

It is rapidly hydrolyzed in the gastrointestinal tract (correct)

It can't cross the blood-brain barrier

It has poor water solubility

What is the effect of introducing a methyl group on the β-carbon of Bethanechol?

Increase in selectivity to muscarinic receptor (correct)

Increase in resistance to hydrolysis

Steric hindrance

Decrease in binding affinity

What is the effect of replacing the nitrogen in acetylcholine with arsenic, phosphorus, or sulfur?

It becomes a more potent antagonist

It becomes a weak agonist (correct)

It has no effect on acetylcholine's activity

It becomes a more potent agonist

What is the importance of the positive charge on nitrogen in acetylcholine?

It is essential for receptor binding Signup and view all the answers

What is the difference in potency between the S-(+)-enantiomer and the R-(–)-enantiomer of methacholine?

The S-(+)-enantiomer is 20-fold more potent Signup and view all the answers

Which of the following is a muscarinic receptor agonist?

Pilocarpine Signup and view all the answers

What is the effect of base-catalyzed epimerization at C3 in the lactone of Pilocarpine?

Formation of a less active stereoisomer Signup and view all the answers

What happens to the S-(+)-isomer of methacholine when it interacts with acetylcholinesterase (AChE)?

It is hydrolyzed by AChE at a slower rate than acetylcholine Signup and view all the answers

What is the effect of introducing a methyl group on the β-carbon of acetylcholine?

It remains equally active Signup and view all the answers

What is the effect of replacing the acetyl group of acetylcholine with a propionyl or butyryl group?

It decreases the potency of the molecule Signup and view all the answers

What is the reason for the greater binding affinity of S-enantiomer of Bethanechol compared to R-enantiomer?

Steric hindrance Signup and view all the answers

What is the characteristic of muscarinic agonists?

They have a sterically hindered methyl group Signup and view all the answers

What is the advantage of Bethanechol over Acetylcholine?

More resistant to hydrolysis Signup and view all the answers

Why is carbachol more resistant to hydrolysis than acetylcholine?

Because it has a less electrophilic carbonyl carbon Signup and view all the answers

What is the effect of replacing the 1-methyl group with a 1-ethyl group in acetylcholine?

It becomes a less active agonist Signup and view all the answers

What is the percentage of Pilocarpine solutions that are subject to hydrolysis if not stored properly?

58% Signup and view all the answers

What is the therapeutic use of carbachol?

It is used to treat glaucoma topically Signup and view all the answers

What is the effect of replacing the acetyl group of acetylcholine with a carbamic acid group?

It increases the potency of the molecule Signup and view all the answers

What is the only available antidote for poisoning by phosphate ester AChEIs?

Pralidoxime (2-PAM) Signup and view all the answers

What is the optimum chain length for anticholinergic activity in Muscarinic Receptor Antagonists?

2-4 C Signup and view all the answers

What is the feature of quaternary ammonium compounds that makes them exhibit most potent anticholinergic activity?

Cationic quaternary ammonium group Signup and view all the answers

What is the difference between atropine and acetylcholine?

Atropine is a tertiary amine, while acetylcholine is a quaternary amine Signup and view all the answers

What is the structure of atropine?

The tropic acid ester of tropine Signup and view all the answers

What is the type of antagonism exhibited by atropine?

Competitive (reversible) Signup and view all the answers

What is the characteristic of Atropine in terms of crossing the Blood-Brain Barrier (BBB)?

It can cross the BBB Signup and view all the answers

What is the characteristic of Tiotropium and Ipratropium?

They are quaternary amines and cannot cross the BBB Signup and view all the answers

What is the mechanism of action of d-Tubocurarine?

It blocks the nicotinic receptor Signup and view all the answers

What is the characteristic of Succinylcholine?

It is a bis-quaternary ammonium compound that is rapidly hydrolyzed Signup and view all the answers

What is the consequence of the quaternary amine structure of Decamethonium?

It cannot cross the BBB Signup and view all the answers

What is the characteristic of Tiotropium and Ipratropium in terms of their activity?

They produce local activity Signup and view all the answers

Study Notes

Muscarinic Receptor Antagonists

Pralidoxime (2-PAM) is the only available antidote for poisoning by phosphate ester AChEIs.
Replacement of H with carboxylic, heterocyclic, aromatic ring, hydroxyl group, or hydroxymethyl group can lead to muscarinic receptor antagonists.
Ester group provides most potent anticholinergic activity, with an optimum chain length of 2-4 C.
Quaternary ammonium compounds exhibit most potent anticholinergic activity, and a cationic quaternary ammonium group is necessary for receptor binding.
Atropine is a naturally occurring alkaloid, isolated from Atropa belladonna and Datura stramonium, and can cross the blood-brain barrier (BBB).
Atropine is a tertiary amine, not ionized under physiological pH, and is the tropic acid ester of tropine.

Muscarinic Receptor Agonists

Acetylcholine (ACh) is the natural agonist, but its duration of action is short due to rapid hydrolysis by acetylcholinesterase (AChE).
Methacholine is a synthetic agonist, more resistant to AChE hydrolysis, and can be administered orally.
Bethanechol is a strong agonist with a chiral center, exhibiting greater binding affinity at muscarinic receptors.
S-enantiomer of methacholine is more potent than R-enantiomer.

Acetylcholine: Structure Activity Relationship

Replacing acetyl group with propionyl or butyryl groups leads to weaker agonists.
Replacing acetyl group with aromatic groups leads to antagonists.
Replacing acetyl group with carbamic acid leads to more potent agonists.
Introduction of a methyl group on the β-carbon increases selectivity to muscarinic receptors.
Introduction of an amino group makes it more resistant to AChE hydrolysis.

Nicotinic Receptor Antagonists

d-Tubocurarine is a competitive antagonist, naturally occurring alkaloid, isolated from South American plant extract.
Decamethonium is a bis-quaternary ammonium compound, with a straight chain analogue of d-Tubocurarine.
Succinylcholine is a bis-quaternary ammonium compound, rapidly hydrolyzed by plasma esterases.

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Description

Test your knowledge on the pharmacology and structure of acetylcholine, including its administration, hydrolysis, and absorption across lipid membranes. Learn about the importance of its quaternary ammonium functional group and its relationship with the blood-brain barrier. Identify agonists and antagonists and more!

Acetylcholine Pharmacology and Structure