Monday, January 08, 2007

Triangle Club**

I wish I had the opportunity to learn more about concepts that are important to understand in developing a functioning drug. Derek's blog will have to suffice for now.
Today I'm posting about Naloxone and Naltrexone. They came up in a conversation about drug addiction (more on that later). These two molecules are opioid receptor antagonists that are strikingly similar in structure, but they're used in the clinic in different ways. An antagonist in the drug sense is something that binds to a receptor and stops the events/actions set in motion by another drug called an agonist. By itself, an antagonist doesn't do anything to the receptor.
(If you're lost and haven't read the links, suffice to say that the word "opioid" sounds like the word "opium" for a reason.)
See here for Molecule of the day's entry on Naloxone.
Naloxone clears your system more rapidly. It's given to patients who have overdosed on things like heroin or morphine. (I think the wikipedia entries I cited above may be confused here..) Naloxone essentially kicks the heroin/morphine off of the opioid receptor, and what you get is a rapid detox, complete with all the very painful symptoms of withdrawal. The detox process is almost instantaneous; the patient goes from completely passed out to completely awake in seconds. The process can also be done under anesthesia.
After detox, patients in rehab may take a once-daily pill of Naltrexone, which is much longer-acting. It'll keep any other opiates they may try to sneak from working.
The difference between the structures is actually really subtle. Note the cyclopropane Naltrexone substitutes for the Naloxone olefin. One extra carbon. Hmmm.
It's known in the literature that cyclopropanes can possess alkene-like reactivity.
What I'm not sure of (and don't have the time to look into in depth) are the differences in how they're metabolized. But here's something about metabolism of cyclopropanes that you can dig out of the literature pretty quickly:
The ref: Chem. Rev. 2003, 103, 1625-1647.

** and if you're into musical comedy and Ivy League tradition, see the Princeton Triangle Club's website.



At 7:46 AM, Anonymous Martin Lersch said...

A short comment on the alkene/cyclopropane similarity: Givaudan's (perfume company) Javanol (perfume ingredient) is a doubly cyclopropanated version of it's alkene "sister". The smell however is quite similar. According to the vibration theory of smell, this is because the molecular vibrations change little when going from a double bond to cyclopropane. Check out this article by Luca Turin for more info on this.

At 8:53 PM, Anonymous Anonymous said...

That is if you buy the vibration theory of odor :-) Maybe it is simply that alkenes and cyclopropanes bind with similar kinetics and thermodynamics. In contrast, there are a some examples (from Firminech) where replacing an alkene with a cyclopropane drops that odor threshold by 100-1000 times (ie, 100-1000 times more potent)

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At 9:33 PM, Anonymous wolfie said...

I need to excuse myself for my last comments. But I still think that I am the greatest blog commenter in the world, although I am not from Princeton nor from Ivy League.

At 9:29 PM, Anonymous wolfie said...

Wow. No I see how I Ivy League works. Masking out everything that does not seem convenient. Typical of arrogant Americans who believe they are the Masters of the Universe. Beware, your Punishment will come soon.


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