Posted by Scott L. Schofield on March 18, 2000, at 13:55:01
In reply to Cam - Anesthestia for Ect, posted by Chris A. on March 17, 2000, at 15:19:35
> I have just started Aricept and my pDoc is having me stop it 48 hours prior to my next treatment. It would be nice to have the donzepil fully on board for neuroprotection. My expert consultant had suggested using curare. My pDoc and I are both a bit shy, so sometimes we don't fully discuss what we should.
Why did he suggest curare? Why not atropine?
The role of these drugs in ECT is not to produce anesthesia, but to temporarily paralyze the muscles so that they don't contract violently during the convulsive phase of post-shock brain activity. You could actually break bones if you don't.
My guess is that having Aricept (donzepil) in the body would exaggerate unpredictably the muscle-relaxant properties of succinylcholine. Muscles are controlled by nerves that use the chemical known as acetylcholine as a neurotransmitter. Succinylcholine is essentially fake acetylcholine, and is an agonist specific to the nicotinic receptor subtype found on motorneurons. Succinylcholine is therefore pro-cholinergic. It accomplishes its muscle-relaxant effect by overstimulating acetylcholine receptors and producing a state of constant depolarization of the nerves that control muscle contraction. These cholinergic nerves become temporarily "fried" and no longer send messages to the muscles to contract.
Donzepil, an acetylcholine cholinesterase inhibitor, is also pro-cholinergic. It tends to enhance cholinergic neurotransmission by preventing the break-down of acetylcholine, thus allowing levels to rise. This is similar to how an MAO-inhibitor works with the monoamines. Increasing the amounts of real acetylcholine plus adding fake acetylcholine (succinylcholine) may be dangerous, or at least have unpredictable effects.
Curare produces muscle relaxation by antagonizing, or blocking the nicotinic acetylcholine receptors. This produces a condition where the nerves remain understimulated and thus do not send messages to the muscle. Curare is anti-cholinergic. Because it binds more strongly to the receptors than does acetylcholine, it doesn't matter that the levels of acetylcholine are increased by donzepil.
I am really not sure why atropine is not being considered. It is used routinely in ECT. Your expert is probably very smart, though. He may be trying to prevent atropine-induced anticholinergic interference with the positive actions of donzepil in the brain. Atropine is an antagonist of the muscarinic subtype of acetylcholine receptor, as opposed to the nicotinic subtype that is affected by curare. Muscarinic receptors in the brain are critical to memory and cognitive function. This is why antidepressants with strong anticholinergic properties can impair these functions. The pro-cholinergic activity of donzepil tends to enhance memory and cognition. Perhaps donzepil would lose its neuroprotective effects (if it has any) if these receptors were blocked.
Sorry. I threw in too much crap. I hope what I wrote isn't too confusing.
Bottom line:1. Succinylcholine + donzepil = too strong.
2. Atropine (and similar drugs) = cancels out positive effects of donzepil
3. Curare = avoids 1 and 2.
4. Atropine serves the purpose.
4. I don't know enough about curare.
- Scott
I should probably get a life.
poster:Scott L. Schofield
thread:27363
URL: http://www.dr-bob.org/babble/20000312/msgs/27484.html