Experimental drug blocks brain chemical

New treatment could help those who aren't helped by other medications

From the Associated Press
September 11, 1998

Washington -- An experimental drug appears to alleviate depression by blocking a mysterious brain chemical -- one that until now, doctors didn't even know was at work in mental disorders.

The finding by Merck & Co., published in today's edition of the journal Science, could give doctors the first entirely new way to treat depression in decades, offering hope to patients who get no help from today's therapies such as Paxil and Prozac.

"This is really very important," said Steven Hyman, director of the government's National Institute on Mental Health, who is familiar with the findings. "To everybody's surprise, it (the new drug) was robustly effective for depression."

The drug still needs more extensive testing in human beings, however, before it would be eligible to receive government approval to be sold.

Depression is the nation's most prevalent mental health problem, afflicting about 15 million Americans at some point in their lives. Americans spend about $3 billion a year on drugs to battle it. Those drugs do help many patients.

But they also can cause serious side effects. Also, some 20% of patients get no help from today's medicines, which all target either serotonin or norepinephrine, brain chemicals called neurotransmitters, Hyman said. So scientists have long hunted another way to attack depression.

Merck says its new drug, code-named MK-869, may do just that, by targeting a brain chemical called substance P that until now has been a mystery.

In a study of 213 patients with moderate to severe depression, Merck tested MK-869 against Paxil, a popular and effective anti-depressant, or against a placebo. During the six-week study, MK-869 relieved depression as effectively as Paxil did, but with fewer side effects, Merck lead researcher Mark Kramer reported in Science.

Just how MK-869 worked inside these patients' brains remains a mystery that has doctors intrigued.

Substance P is a neuropeptide, a small protein that helps nerve cells communicate. It was discovered in 1931, and doctors theorized it might offer a way of treating chronic pain when they learned it played some role in alerting nerve cells to tissue damage. Instead, "it's been a disappointment," Hyman said -- the chronic pain research has failed.

Merck scientists theorized that substance P was playing a role in "emotional pain," based on how animals put in stressful situations to mimic human psychological stress reacted to higher or lower levels of the neuropeptide.

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