I Don't Like the Drugs (But the Drugs Like Me)

It occured to me last night, as I was walking my dogs, that if my neighbor asked me to explain my life right now, I could legitimately say my life revolves around drugs.

Don't get the wrong impression, if you were my neighbor, you might think because there are always a lot of people going in and out of my apartment and staying up late talking, that we do nothing but "party."

The truth is that most of these friends are fellow scientists, studying some aspect of drugs and hoping someday to be employed by a drug company. For example, my biking friend Andrew is singlehandedly making drugs and determining their bioactivity. My good friend Homero studies the toxicicity of drugs by observing DNA damage as a function of drug dose. And I am searching for "natural products," drugs made naturally by plants.

As for me, I used to avoid taking drugs. Something about my upbringing told me that you shouldn't need to rely on external agents to "feel better." I guess that I would say now that pain which prevents you from getting out of bed is a sufficient reason to take drugs. I still tend to take the minimum dose.

The first drug I became comfortable with was Naproxen (available over-the-counter as Aleve). It was prescribed to me after a back injury. I found that it was non-addictive and effective at reducing my pain and inflammation. Those were the ballet days.

Of course when I had a fever, I was given Tylenol (paracetemol, acetomenophen) or Aspirin (acetylsalicylic acid). Other aches and pains, including my Mom's headaches, were treated with Motrin or Advil (ibuprofen).

All of these drugs are in the same class, non-steriodal anti-inflammatory drugs (NSAIDs), which shut down the body's inflammatory signaling pathway. Because each molecular structure is slightly different, each of these drugs has a slightly different interaction with their "target" protein, cyclooxygenase (COX). Looking at their structures below, it is easy to imagine how they could "fit" into a "pocket" created by a much larger molecule. COX is about 350 times more massive than any of these "small molecule" drugs.

Interestingly, NSAIDs (and the substances they are converted to after the body's detoxification has begun) have additional "side-effects." For example, in addition to binding COX, Tylenol's primary metabolite AM404 interacts with the body's cannabanoid system, which is the mechanism responsible for paracetemol's pain relieving properties.

I stuck with non-addictive drugs until I discovered caffeine. ( : Maybe in future blogs I can discuss caffeine and other adenosine receptor antagonists. Other classes of drugs I would like to write about are histamine antagonists and seratonin reuptake inhibitors. Future blog topics of a scientific nature may be on the new wave of "biologics," as recently featured in Chemical & Engineering News, which are the newest revolution in drug development. I found it an engaging topic on a personal level because the article really highlighted the cultural divide between traditional "small molecule" chemists in pharma and those trained in molecular biology and bioanalytical chemistry who are equipped to produce and characterize protein-based drugs.