Two recent articles in Antimicrobial Agents and Chemotherapy demonstrate how most drugs have multiple activities. The antidepressant Prozac was discovered to be an effective antiviral, and another antidepressant, Zoloft, has an antifungal activity. The drugs were included in large chemical libraries that were screened to find compounds with antiviral or antifungal activities.
Researchers at UCLA found that fluoxetine, also known as Prozac, prevents replication of the RNA-carrying coxsackievirus. Prozac is a somewhat controversial treatment for depression. It works by increasing concentrations in the brain of the neurotransmitter serotonin by delaying serotonin recycling. Prozac's newly discovered antiviral property appears unrelated to its ability to inhibit serotonin recycling. Prozac inhibits replication of the coxsackievirus by blocking the virus from making new RNA molecules, which it needs to create new viral particles.
While the antiviral activity of Prozac was being investigated at UCLA, researchers at Texas A&M were screening for chemicals that kill Cryptococcus, which is a type of yeast that can infect the lungs and, in immune compromised individuals, spread to other organs in the body. They found sertraline, the active compound in Zoloft, effectively killed this fungus. As a depression treatment, Zoloft works a little different than Prozac and delays recycling of a whole range of neurotransmitters, including serotonin, but also norepinephrine, dopamine, and others. The researchers publishing this study found that sertraline, the Zoloft chemical, also blocks protein production in the yeast like Cryptococcus, which kills them. Also, Cryptococcus infection can spread to the brain causing meningoencephalitis in immune-compromised patients and many antifungal drug cannot cross the blood-brain barrier. However, Zoloft, obviously, has no problem entering the brain so it may actually be very practical for treatment of this condition.
These studies demonstrate how most drugs have multiple activities. In fact, there has been a lot of recent research efforts to identify alternative uses of already approved drugs. The multiple uncharacterized activities are also the cause of most of the side effects that drugs produce. While it is relatively straightforward to screen and find chemicals that have a certain activity, it is not so simple to characterize all the potential effects a chemical will have on a patient. Of course, potential drug candidate are screened for obvious toxic affects before any clinical trials start, and other serious side effects would hopefully be caught during clinical trials. However, these steps only pick up the most obvious and severe reactions. With the incredibly complicated chemistry of the human body, it is impossible with current technology to know all the responses a drug induces.
Novartis and UCSF recently analyzed approved drugs with a new computer model to try to predict some of the side effects. For the 656 approved drugs they looked at, they found likely interactions with 1,241 proteins that are unrelated to their treatment and known to be related to negative side-effect targets. They were able look at and confirm half these predictions with experimental data. These results show that most drugs have several effects. While they may effectively treat one condition, they are also certainly affecting other aspects of a patient's physiology in unknown ways.
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