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.