'Couch potato pill' may also prevent heatstroke
January 10, 2012, 12:24 am TWN
PARIS--A drug discovered nearly four years ago that builds muscles in "lazy" mice may also prevent heatstroke, according to lab research reported on Sunday.
If further tests confirm the results, the compound could help athletes or soldiers who are so sensitive to heat that they could die from exertion on a hot day, its authors say.
In 2008, a drug known as AICAR became dubbed the "couch potato pill" after it was found to develop muscles and boost endurance among completely inactive laboratory rodents. It is now being explored as a treatment for several muscle diseases and metabolic disorders.
In a paper published by the journal Nature Medicine, researchers in the United States said they discovered by chance that AICAR also protects mice against a disorder called malignant hyperthermia.
This deadly condition is linked to a basket of flaws in a gene called RYR1, a trait which exists in mice as well as humans.
A rise in body temperature causes a leak of calcium in muscle cells, triggering a molecular cascade that eventually makes the muscles contract and break down.
Potassium and protein then pour out of the crippled muscle cells and into the bloodstream, reaching toxic levels that lead to heart or kidney failure.
Tests on mice genetically engineered to have the RYR1 mutation found that AICAR worked perfectly in preventing malignant hypothermia, says the study.
"When we gave AICAR to the mice, it was 100-percent effective in preventing heat-induced deaths, even when we gave it no more than 10 minutes before the activity," said Susan Hamilton, a professor of molecular physiology at Baylor College of Medicine in Houston, Texas.
AICAR — full name 5-aminoimidazole-4-carboxamide ribonucleoside — works by stopping the calcium leak, thus preventing the vicious circle from getting under way.
The finding may lead one day to a drug that would be used preventatively for heat-sensitive young athletes or soldiers in the desert who must wear heavy gear.
Abnormalities in the RYR1 gene are believed to occur in about one person in every 3,000.
But the researchers theorize that the future drug may also work for people without the RYR1 flaw.
"We think the fundamental process that occurs during heatstroke in individuals with RYR1 mutations is likely to be similar to what happens even in their (the mutations') absence," said Robert Dirksen, a professor of pharmacology at the University of Rochester Medical Center in New York.
"The difference may be that individuals with RYR1 mutations are more easily thrust into the process, whereas those without (the mutations) need to be pushed more — for example, by exposure to even greater temperatures or a long time, in order to move beyond a critical threshold."