MadSci Network: Biochemistry

Re: What are the long term effects of Cholinesterase inhibitors.

Date: Thu May 11 22:26:21 2000
Posted By: Phyllis Pugh, Post-doc/Fellow, Neurobiology, Medical College of Ohio
Area of science: Biochemistry
ID: 957284856.Bc

Hi David,

That's a really good and appropriate question, especially given both your background and some of the current questions being asked in biology. I'm sorry that this took so long to get back to you, but I wanted to make sure I got things correct. I have to confess that, although I am a neurobiologist who works on acetylcholine receptors, I don't work directly on acetycholinesterase (AChE) or its inhibitors (AChEIs) (although I use them in the laboratory). Also, I should mention that I'm not an M.D., so I will try to answer your questions, but a doctor might be better (and I'll point you to some places where you could likely talk to one).

First, I'm going to answer your direct question-- why would it build up a "surplus" instead of acting to kill. Like many drugs, it is simply a matter of dosage. Small amounts can do one thing (and the body can compensate), while larger amounts have deleterious effects. While I have not found any specific references on the mechanism of the AChEIs protection, I believe that what is going on is that by making the body "think" that it is low on AChE. Since your body's function relies on its ability to maintain homeostasis (or keep things at the same levels to the best of its ability), then it upregulates the production of AChE to compensate for this. Well, the type of AChEI that you took (which I think is actually pyridostigmine bromide -- PB) doesn't permanently block the AChE, therefore when PB is released from the AChE molecule, there is now an excess of AChE activity--protecting the body from the having some portion of the AChE shut down (which would result in what you have read about).

Now, I did a bunch of reading up on things about long term effects of exposure to such agents. Basically, of the long term studies which have been done, few adverse effects have been seen. It's worth mentioning that AChEIs are used clinically in the treatment of Alzheimer's Disease and Myasthenia Gravis. In both of these diseases, the acetylcholine receptors are compromised (either degraded or lost in some manner), and AChEIs are used to increase the ACh levels at the synapses, allowing fewer receptors to do the job (at least partially). Given these uses, it appears that long term studies under those conditions are ongoing.

Okay, now for some places where I found information and your can find more information:

I'm making the assumption that since you say you are an undergraduate that you can find some of these things in the library or med school library nearby (they weren't available in ours).

I hope this helps. Feel free to ask a followup question if there is anything more we can do.


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