What is the Difference Between Reversible and Irreversible Anticholinesterase

The key difference between reversible and irreversible anticholinesterase is that reversible anticholinesterases bind to AChE non-covalently, and the enzyme can regain its function over time, while irreversible anticholinesterases bind to AChE covalently, and the enzyme is permanently inactivated leading to prolonged effects.

Acetylcholinesterase (AChE) inhibitors or anticholinesterase inhibit the cholinesterase enzyme from breaking down acetylcholine (ACh), increasing the neurotransmitter action level and their existence. ACh is a neurotransmitter that plays a role in many important bodily functions, including muscle contraction, memory, and mood. AChE inhibitors are divided into irreversible and reversible based on the mode of action. Reversible inhibitors, also known as prosthetic anticholinesterase, are reversible, competitive, and have a short duration of action. Therapeutically used reversible inhibitors can be classified as either competitive or non-competitive. Conversely, irreversible AChE inhibitors are linked to toxic effects. These compounds are typically not used for medical or therapeutic purposes, as they are more commonly used in pesticides and associated with chemical warfare agents.

CONTENTS

1. Overview and Key Difference
2. What is Reversible Anticholinesterase
3. What is Irreversible Anticholinesterase
4. Similarities – Reversible and Irreversible Anticholinesterase
5. Reversible vs. Irreversible Anticholinesterase in Tabular Form
6. FAQ – Reversible and Irreversible Anticholinesterase
7. Summary – Reversible vs. Irreversible Anticholinesterase

What is Reversible Anticholinesterase?

Reversible anticholinesterases are drugs that temporarily inhibit the activity of AChE by binding to AChE and preventing it from breaking down ACh. This results in increased levels of ACh in the body, prolonged muscle contractions, and improved memory and cognition, allowing them to be used in various pharmacological applications. Furthermore, these inhibitors are found in different forms, such as those with carbamate, quaternary, or tertiary ammonium groups. They have been treated with various diseases, including Alzheimer’s disease, myasthenia gravis, bladder distention, glaucoma, postoperative ileus, and anticholinergic overdose.

Reversible anticholinesterases are generally safe and well-tolerated, but they can cause some side effects, such as nausea, vomiting, diarrhea, and headache. Examples of reversible anticholinesterases include Donepezil, Rivastigmine, Physostigmine, Neostigmine, and Pyridostigmine.

What are Irreversible Anticholinesterases?

Irreversible anticholinesterases are drugs that covalently bind to the AChE, preventing it from breaking down Ach. Due to their irreversible nature, they overstimulate cholinergic receptors, leading to toxicity and serious effects on the nervous system. These compounds are usually associated with pesticides and chemical warfare agents and are not typically used for medical or therapeutic purposes. Sarin and other nerve agents work by irreversibly inhibiting cholinesterase enzymes, leading to a buildup of acetylcholine at synapses and causing a range of severe symptoms, including muscle twitching, seizures, respiratory distress, and death if not treated promptly with antidotes like atropine and pralidoxime.

These chemicals are extremely toxic and dangerous, and their use is regulated by international treaties such as the Chemical Weapons Convention due to their potential to cause mass casualties and harm. However, compounds such as Echothiophate are used for the treatment of glaucoma.

What are the Similarities Between Reversible and Irreversible Anticholinesterase?

• Reversible and irreversible anticholinesterases work by inhibiting acetylcholinesterase.
• Despite their names, reversible and irreversible anticholinesterases can exhibit some reversibility.
• They can be toxic if used in excessive amounts or inappropriately.

What is the Difference Between Reversible and Irreversible Anticholinesterase?

AChE inhibitors are classified as reversible and irreversible based on their mode of action. Reversible anticholinesterases bind to the AChE non-covalently, suggesting the bond can be broken and the enzyme can regain its function over time. This typically occurs within minutes to hours. In contrast, irreversible anticholinesterases bind to AChE covalently; therefore, the bond cannot be broken, and the enzyme is permanently inactivated. This can lead to prolonged effects, lasting for days or even weeks. Another key difference between reversible and irreversible anticholinesterase is their toxicity. Irreversible anticholinesterases are generally more toxic than reversible anticholinesterases because they cause more prolonged and severe inhibition of AChE. Therefore, reversible anticholinesterases are used in the medical field, while irreversible anticholinesterases are typically used as pesticides, insecticides, and nerve agents in warfare.

Below is a summary of the difference between reversible and irreversible anticholinesterase in tabular form for side-by-side comparison.

FAQ: Reversible and Irreversible Anticholinesterase

What are the reversible anticholinesterase drugs?

Reversible anticholinesterases bind to AChE non-covalently, and the enzyme can regain its function over time.

What are the examples of irreversible anticholinesterase drugs?

Examples of irreversible anticholinesterase drugs include organophosphate compounds, Sarin, and Echothiophate.

What are anticholinesterase drugs for?

Anticholinesterase drugs inhibit the cholinesterase enzyme from breaking down acetylcholine (ACh), increasing the neurotransmitter action level and their existence.

Summary – Reversible vs. Irreversible Anticholinesterase

The key difference between reversible and irreversible anticholinesterases lies in their mechanism of action and duration of effects. Reversible anticholinesterases bind to AChE non-covalently and have a temporary inhibitory effect, while irreversible anticholinesterases bind to AChE covalently, resulting in permanent inactivation and prolonged effects. Reversible anticholinesterases are commonly used in medical treatments for various conditions, while irreversible anticholinesterases are primarily associated with pesticides, insecticides, and chemical warfare agents due to their high toxicity. This is the key difference between reversible and irreversible anticholinesterase. However, it’s important to remember that both types can be toxic when used inappropriately.

Reference:

1. Colovic, Mirjana B., et al. “Acetylcholinesterase inhibitors: Pharmacology and toxicology.” Current Neuropharmacology, vol. 11, no. 3, 2013, pp. 315–335.
2. Arbuthnott, Gordon, and Marianela Garcia-Muñoz. “Neuropharmacology.” Companion to Psychiatric Studies, 2010, pp. 45–76.

Image Courtesy:

1. “Acetylcholinesterase Inhibitors” By Physicist – Own work (CC BY-SA 4.0) via Commons Wikimedia