umans have been “repurposing” for centuries. Today we turn old churches into museums, schoolhouses into condos, old tires into artificial turf, and plastic bottles into dress pants. Drugs have become a new and exciting target for this activity.
Two high-profile examples in the drug world are sildenafil and minoxidil. Both began as medications for cardiovascular issues. But along the way, it became clear that they did other things even better. Sildenafil, rebranded as Viagra, helps some men with erectile dysfunction get and sustain erections. Minoxidil helps hair grow, which spawned Rogaine.
Finding new uses for existing medications makes good sense. The cost to develop a new drug is astounding, ranging from $1 billion to $2 billion, and it takes 10 to 12 years or more to go from the lab to the clinic. Only about 10 percent of new drugs and biologics are approved, and fewer than 20 percent of them generate enough revenue to cover the cost of research and development.
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Repurposing can save time and money in developing treatments for diseases that don’t have effective therapies. Another advantage is that the side effects of the “old” drug are already well-known.
A new life for ketamine
Fifty years ago, I was part of a team at Parke-Davis (once America’s oldest and largest pharmaceutical company) that developed a new drug called ketamine as an anesthetic agent. The FDA approved it in 1970. I’ve been keeping an eye on this medication ever since. Ketamine blocks a glutamate receptor known as NMDA. This receptor is involved in pain transmission and other activities of the central nervous system, including memory, cognition, and sensory functions such as hearing.
My research team at the Texas A&M Health Science Center is one of several looking at ketamine for new uses, such as treating tinnitus (ringing in the ears), major depression, and chronic pain. Chronic pain and depression often coexist; when depression improves, people often tolerate pain better.
No drugs are currently approved to treat tinnitus. It affects more than 15 million Americans, including soldiers who have been on the battlefield, teenagers who use headphones at high volumes, industrial workers who experience high levels of ambient noise, and the elderly. Ketamine could be a safe treatment for this potentially aggravating condition.
Although numerous drugs are available to treat depression, they don’t always work. Antidepressants like Prozac, Zoloft, or Effexor can take weeks or months to ease depression, if they work at all. Ketamine acts quickly to relieve depression and ease suicidal thoughts, often having effects in minutes to hours.
Opioids such as morphine are powerful painkillers, but they can make a spinal cord injury worse. Sometimes they can even make pain worse. Opioids also can be addictive. Ketamine, despite its use as a street drug, isn’t thought to be addictive, but it might be habit-forming.
We plan to test ketamine in combination with another existing drug, brimonidine, which is currently approved to treat glaucoma and rosacea. Our hope is that this combination will be better than ketamine alone for treating pain while canceling out negative side effects of each other.
There are a number of other promising candidates for repurposing: mecamylamine, ropinirole, and valsartan were all originally used for high blood pressure but are now being examined for treating depression, Parkinson’s disease, and Alzheimer’s disease, respectively. Tamoxifen, originally used for breast cancer, and amphotericin B, an antifungal drug, might both be useful in bipolar disorder.
As is the case for any drug, new or repurposed, there is always more to learn. But it makes sense to explore existing drugs for new indications as a way to improve treatment while reducing drug development time, cost, and risk of unexpected side effects.
David E. Potter, PhD, is professor and chair of pharmaceutical sciences at the Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy.