Source: AMC news release
Date: 12 August 2003

Albany Med Receives $900,000 to Study Pain Relievers

ALBANY, N.Y., August 12, 2003 – Lindsay Hough, Ph.D., professor and associate director of the Center for Neuropharmacology and Neuroscience at Albany Medical College, has been awarded a four-year, $900,000 research grant from The National Institute on Drug Abuse to continue his work on the development of new pain relievers.

“It has only been appreciated recently that the brain has its own marijuana-like chemicals—called endocannabinoids—that it appears to use to relieve pain,” Dr. Hough says. The drug, improgan, which Dr. Hough discovered and has been studying for seven years, may be the first in a class of drugs that can use natural endocannabinoids for therapeutic potential.

Dr. Hough has been busy trying to figure out exactly how improgan works in the brain. Now he and his colleagues will be tackling the problem from an additional angle--designing and testing a new series of drugs based on improgan with the eventual goal of developing a medication that will be clinically useful.

“We have published about 20 papers on improgan. It appears to be a powerful pain reliever without the side effects of morphine or marijuana, but with its own limitations, such as it can only be directly injected into the brain and therefore is only useful in a laboratory setting,” explains Dr. Hough. “Now we are in the process of slightly altering the chemical structure of improgan to create new drugs which may be more useful to patients someday.”

Many consider morphine and similar opiate drugs to be godsends for patients in pain, but they can cause severe constipation and respiratory depression. Patients taking morphine regularly also become tolerant of it, so larger and larger doses need to be used, increasing the risk of side effects. And, opioids like heroin also have abuse liability, which explains why the National Institute on Drug Abuse is interested in Dr. Hough’s research on non-opioid pain relievers.

Unlike pain relievers such as aspirin and acetaminophen, which work by inhibiting the body's production of pain-producing prostaglandins, morphine and other opiate drugs act on opioid receptors in the brain--neurotransmitter receptors responsible for pain killing.

“Another class of drugs that stop pain by working on receptors in the brain are the cannabinoids, of which marijuana is the most infamous,” says Dr. Hough. He explains that these drugs act on the cannibinoid receptors to stop pain. “However, again, drugs in this class also have unwanted side effects, the ‘munchies’ being just the tip of the iceberg. Seriously, while they have great potential as pain relievers, that has been overshadowed by their tremendous abuse potential.”

Improgan and its cousins are not exactly cannabinoid, or marijuana-like drugs, and, truth be told, they do not appear to be acting on the same receptors, but Dr. Hough says recent studies show they seem to be somehow tapping into the brain’s own pain relieving system related to the cannabinoid receptors. “This hasn’t been shown before. The beauty of it is they appear to be working as well as cannabinoids in relieving pain, but without the side effects of cannabinoids like marijuana,” he says.

However, he points out that he has not been able to find out exactly what receptor improgan is acting on. The receptor for a drug is a protein in the body that first recognizes the drug, allows the drug to bind to it and initiate biological signals. “The receptor is the lock that the drug molecule—the key—fits into,” he says. “We’ve measured all these interesting changes in the brain that occur after taking the drug, but we haven’t found the initial point where the drug is acting yet. While we know it has pain relieving effects, we really need to figure that out because we can’t turn a drug into a successful pharmaceutical product without that piece of information.”

“Over the next four years with this large grant, we are charged with continuing to figure out just what receptor this drug is acting on, and with finding out if we can make a useful drug by modifying the chemical structure, ” Dr. Hough says.

Hough and his collaborators have now made and studied nearly 40 new improgan-like compounds by changing the drug’s chemical structure. The research team includes Julia Nalwalk, Lesley Powell, Konstantina Svokos, Brian Kern, graduate students Keri Cannon and Rebecca Stadel, and medical student Neil Gehani. Hough’s collaborators include chemists Mark Wentland, Ph.D., from Rennselaer Polytechnic Institute, and Rob Leurs, Ph.D., of the Leiden/Amsterdam Center for Drug Design in the Netherlands.
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