What Causes the Bad Reaction?
Because the Flagyl-alcohol reaction is said to resemble the Antabuse-alcohol reaction, researchers originally assumed that they work the same way. Ordinarily, the liver breaks down ethanol in two steps: first into acetaldehyde, then into acetic acid. Antabuse inhibits the second step, causing levels of acetaldehyde in the blood to rise. The increased blood acetaldehyde causes the acute symptoms of vomiting, flushing, etc.
More recent research has shown that Flagyl does not inhibit the breakdown of acetaldehyde, and that blood acetaldehyde does not increase when Flagyl and alcohol are combined. Therefore, some other mechanism must be at work. One set of researchers (Karamanakos et al. 2007) suggested it may be related to increased serotonin because they were able to show that Flagyl increases brain serotonin in rats.
Another set of researchers (Visapää et al. 2002) noted that there are only ten human case reports of a bad Flagyl-alcohol reaction and suggested that the problem may not be as common as previously thought. They did, however, note that it is possible that this "reaction can occur in some subgroups," so it is still wise to avoid mixing Flagyl and alcohol.