[MEDORG-SEMIS-04-PT1] CHOLINERGIC

THIS FLASHCARDS IS ABOUT [MEDORD] CHOLINERGIC - MUSCARNIC AGONISTS.

Cholinergic Agents

These influences the parasympathetic nervous system by interacting with acetylcholine (ACh) pathways.

Supplemental Info Only

Acetylcholine in the natural neurotransmitter responsible for:

• Decreased heart rate

• Increased gland secretion

• Increased gastrointestinal motility

• Bronchoconstriction

• Miosis (pupil constriction)

Supplemental Info Only

Cholinergic drugs either:

1. Activate cholinergic receptors

2. Block cholinergic receptors

3. Increase acetylcholine concentration

4. Restore acetylcholinesterase activity

Acetylcholine

The pharmacophore of muscarinic agonists resembles what?

Supplemental Info Only

The pharmacophore resembles acetylcholine.

Essential structural elements:

1. Quaternary ammonium group

2. Ester group

3. Two-carbon linker

4. Small alkyl substituents

General structure: (CH3)3N+ — CH2 — CH2 — O — C(=O) — R

(The positive charge is crucial for receptor binding)

1. Small alkyl groups

2. Antagonist

SAR OF MUSCARINIC AGONISTS

• Nitrogen Substitution
  - (1) These groups on nitrogen are required
  - Large groups decrease agonist activity and may convert the molecule into an (2)_____.

Two carbon atoms

What is the optimal spacing between nitrogen and ester?

(Changes in distance reduce receptor affinity)

Hydrolysis by acetylcholinesterase

The ester portion is important for receptor binding but is also the site of?

Supplemental Info Only

Drug Design Strategies (Ester Group):

• Steric hindrance

• Carbamate formation

(To slow hydrolysis)

• Methacholine

• Bethanechol

• Pilocarpine

What are the (3) Muscarinic Agonists?

Hint: ME-BE-PI

B-methyl substitution

What is the substitution of methacholine?

Effect:

• Increased muscarinic selectivity

• Slower hydrolysis

Bronchial challenge test

What is the clinical use of methacholine?

1. Carbamate

2. B-methyl group

Structure Modification of Bethanechol:

• (1)_____ instead of acetate

• (2) What is the group?

Acetylcholinesterase

Consequences of Bethanechol Structure Modification:

• Resistant to ___________

• Longer duration

Urinary retention

Bethanechol is used for?

Alkaloid

Unlike other agonists, pilocarpine is an?

Supplemental Info Only

Structural Features of Pilocarpine:

• Imidazole ring

• Tertiary amine

(Because it is a tertiary amine, it can penetrate tissues easily)

• Xerostomia

• Glaucoma

Pilocarpine is used for (2)?

Hint: XG

Xerostomia

This is the subjective sensation of dry mouth, which may be associated with reduced or altered salivary flow.