Scientists have discovered what could be the ultimate workout for couch potatoes: exercise in a pill.

In experiments on mice that did no exercise, the chemical compound, known as AICAR, allowed them to run 44 percent farther on a treadmill than those that did not receive the drug.

The drug, according to the researchers, changed the physical composition of muscle, essentially transforming the tissue from sugar-burning fast-twitch fibers to fat-burning slow-twitch ones – the same change that occurs in distance runners and cyclists through training. The researchers said the drug's fat-burning ability could also help reduce weight, ward off diabetes and prevent heart disease – the benefits of daily aerobic activity without the perspiration.

The study was published Thursday in the journal Cell.

"It's an amazing piece of pharmacology," said David Mangelsdorf, a pharmacologist at University of Texas Southwestern Medical Center in Dallas, who was not connected with the research. "You're getting the benefits of exercise without having to do any work."

They also report that in mice that did exercise training, a second drug called GW1516 made their workout much more effective at boosting endurance. After a month of taking that drug and exercising, mice could run 68 percent longer and 70 percent farther than other mice that exercised but didn't get the drug.

It is unknown if AICAR has any benefit for athletes who actually work out – or if either drug helps human endurance for that matter, since the research has so far only involved mice.

"The mouse doctors and cell biologists are of course quite enthusiastic about these things, but the human doctors are a little more reticent," said Dr. Benjamin Levine, a cardiologist who leads the Institute for Exercise and Environmental Medicine at Presbyterian Hospital of Dallas, and who was not involved in the study.

But lead researcher Ronald Evans, a molecular physiologist at the Salk Institute for Biological Studies in the San Diego community of La Jolla, said he has already been contacted by dozens of athletes and overweight people who have heard about his research from several lectures he has given on the subject. With more research, Dr. Evans said, the drug might one day be used as a treatment for muscle wasting, obesity and as a means of allowing bedridden patients to reap the benefits of exercise.

The drug has been tested in humans for a variety of conditions related to the heart and repeatedly passed basic safety tests.

"It was found to be a quite safe drug, at least at the doses we were using," said chemist Paul Laikind, who patented the compound in the 1980s and began testing it as a means of preserving blood flow to the heart during surgery.

The compound is now owned by drug maker Schering-Plough Corp., which is trying to develop the compound as an intravenous infusion for the prevention of a complication of bypass surgery.

The discovery of AICAR as a potential couch potato exercise pill grew out of Dr. Evans' continuing research on creating super mice. By injecting a single gene into the nucleus of a fertilized egg, he created mice born with more efficient muscles, faster metabolisms and stronger hearts.

He wanted to know if it were possible to achieve the same effect using a drug.

His team didn't start with AICAR, but with GW1516.

In sedentary mice, the drug had no effect on endurance. Only when the drug was combined with exercise did it give the mice an advantage.

When the researchers dissected the mice that got the drug, they found that the number of high-efficiency muscle fibers had increased 29 percent.

Then Dr. Evans decided to try AICAR. When sedentary mice that got the drug daily for four weeks were placed on a treadmill, they were able to run an average of about 550 meters, 44 percent farther than mice that had received a placebo.

Los Angeles Times,

The Associated Press