Scopolamine where is thy sting?

What happened to all the chemistry?  The short answer is that I got sick a week or so ago with a bad head cold.  I don’t know how you are with a head cold, but when I get them every 5 or so years my head (and brain) feel like they’re  packed with seaweed and my thought processes approach the glacial. I’d far rather be posting comments on the excellent Anslyn and Dougherty as I go through it, but learning new chemistry is simply beyond me.  So I shifted gears and have spent the last week going through a few chapters of a book on something even harder — Galois theory and reading the journals I get and taking a few notes.

So if you can ‘t write about what you’re learning, write about what you know — in this case, medicine, pharmacology and neuroscience. I think some of the upcoming posts will be of interest to organic chemists and medicinal chemists (even this post).  Everyone likes looking over the Doctor’s shoulder, so some of my clinical experience with opiates (and the drugs described below) should be interesting.

My internist prescribed an inhaler of tiotropium to get rid of a nocturnal cough which has prevented decent sleep since I got sick.  Here’s a link to the structure.   For what follows, a look at wouldn’t hurt.   Tiotropium and two of its friends I’m about to discuss block the activity of a neurotransmitter — acetylCholine at the muscarinic subclass of its receptors.   This will (hopefully) stop the nocturnal coughs and the use of oxycodone — a narcotic like codeine — which is incredibly effective against cough (far better than anything you can buy over the counter).  I’ll talk about side effects in another post, but at 3 AM after coughing for an hour or so you are quite willing to accept them.

My brother’s an internist.   We both agree that every doc should get sick now and then.  Sure we know what patients go through intellectually, but experiencing some physical discomfort (or fear) gives you a perspective that watching and thinking simply does not.

Now the chemists among you should take a look at Atropine and Scopolamine  Too bad I don’t know how to get chemical structures into the posts.  Test your memory.  Having looked briefly at atropine and scopolamine — can you tell me what the difference is? It’s amazingly subtle — scopolamine is an oxirane, and atropine isn’t.  One lousy oxygen.

Yet the drugs are used quite differently.  Scopolamine is far more likely to cause delirium and psychosis than atropine.  Feminists — get ready to shudder.  Scopolamine was extensively used in obstetrics ’64 – ’66 (or at least it was at the time in the Ivy League med school I went to).  Why?  It drove women in labor out of their skull, but afterwards they remembered nothing.  Scopolamine simply prevents you from putting current events (or facts) into memory.  It was quite something to see a society matron of impeccable breeding and refinement,  walking around the OB floor naked and raving.  When it came time for my two kids to be born, I made sure my wife had a caudal, and no scopolamine thank you.

That’s fortunately in the past, but drugs that block muscarinic acetyl choline receptors are in wide use.  I long ago gave up ever using Artane (which has some muscarinic antiCholinergic activity) for anyone over 80 with Parkinsonism.  It worked pretty well for tremor,  but after a week or two their memory was shot.

Incidentally the profound effect on memory of blocking acetyl choline at muscarinic receptors led to the idea that increasing it there would help people remember. Since the neurons supplying acetyl choline to the cerebral cortex are found in a small group of neurons at the base of the brain (the basal nucleus of Meynert) which degenerate early on in Alzheimer’s disease, methods were sought to increase acetyl choline levels in the brain.  What was settled on was a class of drugs which blocked the breakdown of acetyl choline (called anticholinesterases as acetyl choline is a simple ester) See  Despite a lot of hype (particularly by academics) neither yours truly or any clinical neurologist of my acquaintance ever saw anything dramatic happen with this drug class (Cognex is an early example).

Presumably the tiotropium bromide I’m to inhale once a day won’t fry my brain (or put me in urinary retention, another side effect).  My wife is keeping a close watch.

Stay tuned — the next post will tell you why we’ll never have a drug which will block addiction.

Also: if anyone out there can tell me how to get structures into WordPress without essentially saying RTFM (which I don’t have time to do), please leave a comment.

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  • luysii  On April 20, 2011 at 9:15 am

    I happened to look at what dextromethorphan (a cough suppressant which has a ring structure very close to morphine but which is INactive at the opiate receptors) actually does. It blocks the NMDA receptor (thought to be important in learning, and certainly important in long term potentiation in animals, assuming that has anything at all to do with the way humans learn). Oy Vey

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