Researchers find brain pathway for drugs

By William McCall

Associated Press

PORTLAND, Ore. — A faint signaling system that allows a tiny number of brain cells to "talk" to each other may be the path for synthetic drugs such as Ecstasy to affect larger systems that control mood and even body temperature or blood pressure, researchers say.

Scientists hope their discovery will help them find a way to block the effects of Ecstasy and other methamphetamines.

Oregon researchers found the "trace amines" receptor system by using a form of reverse engineering to track down chemical signals so faint that one scientist said it makes "finding a needle in a haystack look easy."

"I think this is one of the most significant findings we’ve seen emerge in a long time," added Nancy Pilotte, a neurological researcher at the National Institute of Drug Abuse in Washington, D.C.

The Oregon Health &Science University study was led by David Grandy, who was looking for receptors for the neurotransmitter dopamine, one of the main messenger chemicals in the brain.

"To be honest, we weren’t looking for this particular receptor," Grandy said. "But when we saw it, we knew we had something."

Amines are a broad category of molecules that combine carbon and nitrogen to take on a variety of shapes and forms, such as the rings that make up nicotine or morphine, or chemical messengers in the body such as dopamine, or waste products from the decay of protein in rotting flesh.

Trace amines also are found in some foods, including chocolate, hard cheeses, red wine and beer.

The discovery of a receptor for trace amines confirms the suspicions of medical researchers who have searched for the source of central nervous system activity they could not otherwise explain, Grandy said.

Previously, such receptors and signaling systems had been found only in insects, he said.

"It gives us a whole new way to track the pathway of drugs like Ecstasy and methamphetamine," he said. "Everybody thought they had a good idea how those drugs work, and now we’ve got something entirely new to consider."

Ecstasy, known scientifically as methylenedioxymethamphetamine, or MDMA, is similar to other synthetic drugs such as methamphetamine and mescaline, which can cause brain damage.

Ecstasy typically induces feelings of euphoria, increased energy and sexual arousal. But it also suppresses appetite, thirst and the need to sleep, and in high doses can sharply increase body temperature, leading to kidney and heart failure and death.

"This receptor could be mediating some of those effects of Ecstasy," Grandy said.

The Oregon researchers say the trace amine system also may be involved in other normal body functions, such as blood pressure regulation, as well as diseases such as diabetes, migraine headaches, schizophrenia, anxiety and depression.

Pilotte said the study is especially important because it shows that cell signaling systems operating at extremely low levels and in highly specific areas of the brain or body can have such a large effect.

"This is really cool stuff that I think could open up a lot of exciting research," Pilotte said.

Grandy plans to present his study next week at the annual meeting of the American College of Neuropsychopharmacology. The results also are being published in the December edition of the journal Molecular Pharmacology.