Factors Affecting Methacholine Activity

What is the primary effect of a β-substitution on the activity of acetyl-β-methylcholine?

According to the five atoms rule, what is the optimal separation of the ester group from the onium moiety for maximum muscarinic activity?

How does replacing methyl groups with larger alkyl groups affect the activity of methacholine?

What occurs when methyl groups are successively replaced with hydrogen atoms?

What effect does an ethylene bridge have on methacholine's structure?

Factors Affecting Acetyl-β-methylcholine (Methacholine) Activity

Substitution on the choline moiety impacts both nicotinic and muscarinic activity.
- Substitution decreases both activities, but muscarinic activity experiences a greater decrease.
- A β-substitution has a more significant effect on nicotinic activity compared to muscarinic activity.
Optimal separation of ester groups and onium moiety is key.
- Shortening or lengthening the separation between the ester group and the onium moiety reduces muscarinic activity.
- "Five atoms rule" indicates optimal separation is around five atoms, with activity loss outside this range.
Methyl group size impacts activity.
- Increasing methyl group size reduces activity by 25%.
- Replacing methyl groups with larger alkyl groups (e.g., ethyl) significantly drops activity, with complete loss after introducing two or more larger alkyl groups.
- Triple replacement of methyl with ethyl groups creates an antagonist.
Position of substituents affects muscarinic activity.
- Successive replacements of methyl groups with hydrogen atoms (towards tertiary, secondary, and primary amines) decrease muscarinic activity.
- This effect is more pronounced with each successive replacement.
Ethylene bridge optimizes spacing.
- An ethylene bridge serves as a "perfect spacer".
- It optimizes spacing with a maximum of four atoms between the ammonium and terminal methyl group.

This quiz explores the various factors influencing the activity of Acetyl-β-methylcholine (Methacholine) with a focus on the effects of substitution, optimal separation of ester groups, and methyl group size. It examines how these factors impact both nicotinic and muscarinic activities, offering insights into their biochemical significance.