Metronidazole (C
6H
9N
3O
3) is an antibacterial and antiprotozoal agent that has gained widespread use as a
drug. It is classified as a
nitroimidazole, and it is a synthetic derivative of
azomycin. It is sold in the
United States as
Flagyl.
History
Metronidazole was first used against
parasites such as
Trichomonas vaginalis and
Entamoeba histolytica. The antibacterial activity of
metronidazole was discovered purely by
accident in
1962 when a patient was cured of both
trichomoniasis and bacterial
gingivitis, and since then, the use of
metronidazole has skyrocketed.
Metronidazole has remained popular because it is
inexpensive, has good tissue penetration, and has relatively mild side effects.
Metronidazole is also effective against a wide variety of
pathogenic critters, such as
Trichomonas vaginalis,
Entamoeba histolytica,
Giardia lamblia,
Clostridium difficile, and
Helicobacter pylori.
1
However, the
mechanism by which
metronidazole works has until recently been poorly understood, and even today some questions linger. This is probably because, in the past,
noone really cared as long as it worked, but as concerns about
resistance to
metronidazole are beginning to surface in the scientific community, a need for research into the matter has been recognized.*
Trends
Metronidazole-sensitive organisms all live under
anaerobic conditions, and the more complex
parasites all lack
mitochondria,
centrioles, and
introns. This implies that
metronidazole is activated by
enzymes specific to
anaerobic organisms, and this notion has been upheld by various findings. For instance, researchers have shown that
metronidazole acts against
Trichomonas vaginalis by binding to a
protein called
Trichomonas vaginalis ferredoxin (hereafter referred to as TvFd), a protein that is found in the
hydrogenosome of the
protozoan and is a component of the creature's
electron transport pathway.
Mechanism
It was originally thought that
metronidazole was a
protein inhibitor and disrupted essential
metabolic pathways, but experiments have
squashed this idea. Research shows that
metronidazole is
activated when it
gains an electron from the
molecule that activates it. In the case of
Trichomonas vaginalis, that
molecule is TvFd.
It has been proven experimentally that upon gaining an
electron,
metronidazole becomes extremely reactive and destroys cellular
DNA. However, the exact mechanism by which
metronidazole is
reduced has not yet been
elucidated.**
Risks, or Possible Causes for Concern
Side Effects
Metronidazole will often cause stomach cramps, dizziness, headache,
diarrhea,
nausea or vomiting. If it causes numbness, tingling, or
convulsions, you should check with your doctor immediately.
1The use of metronidazole against gastritis caused by Helicobacter pylori is a component of combination therapy used to treat the condition.
*The issue of resistance to metronidazole is currently a fairly minor concern, but some scientists worry that the widespread use of treatments which use only metronidazole will eventually lead to problems.
**I have recently been using computer simulations to research the mechanism by which metronidazole is reduced by TvFd. Much of the information I put in this writeup was taught me by my supervisor at the beginning of the project. I have not included specific details of this project because it would require a long explanation of some of the characteristics of TvFd, and that is not the subject of this writeup.
References, or just more reading:
http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202365.html
Petrin, D., K. Delgaty, R. Bhatt, and G. Garber. 1998. Clinical and microbiological aspects of Trichomonas vaginals. Clin. Microbol. Rev. 11:300-317.
or online at
http://cmr.asm.org/cgi/content/full/11/2/300
Sameuelson, John. 1999. Why Metronidazole Is Active against both Bacteria and Parasites. Antimicrob. Agents Chemother. 43: 1533-1541.
or online at
http://aac.asm.org/cgi/content/full/43/7/1533
These papers have their own references as well.