Released Sunday, March 29 1998 at the national meeting of the American Chemical Society
For more information, contact: Kara Villamil, or Mona S. Rowe
DALLAS - Just like humans can have a preferred hand for writing, drug molecules can be "lefty" or "righty," too. But unlike humans, a drug's "handedness" may make the difference between having the desired effect and being completely inactive in the body.
Yu-Shin Ding, a chemist at the U.S. Department of Energy's Brookhaven National Laboratory, along with her colleagues Joanna Fowler and Nora Volkow, have found that handedness counts in pharmaceuticals like Ritalin, used to treat attention deficit disorder (ADD) in children, and in illegal drugs like cocaine. That finding was reported today at the American Chemical Society's national meeting.
Using a medical imaging technique called positron emission tomography (PET), Ding and her team have been able to track the activity of different "handed" drugs in the brain, and establish that there are differences in the physical activity of the different forms of the same molecule.
Most drugs are actually mixtures of the "lefty" and "righty" versions of the same molecule. A molecule takes on a "handedness" depending on the orientation of its structure - a left-handed molecule is the mirror image of a right-handed molecule.
In the case of Ritalin, known also as methylphenidate, they have found that the right-handed version, or enantiomer, does most of the work - 10 times more than the left-handed molecule.
Meanwhile, the left-handed version has trouble binding to the receptors on brain cells that help control the movement of the communication chemical dopamine between neighboring cells. The dopamine system is Ritalin's main target, and the drug's effect on the flow of dopamine helps ease the symptoms of ADD children who take it.
Currently, manufactured Ritalin contains both the left- and right-handed molecules - what chemists call a "racemic" mixture. But, says Ding, if the beneficial effects of the drug reside only in the right-handed version, then 50 percent of the weight of the administered drug may not contribute to its therapeutic effects, or may even affect the active form's behavior or contribute to its side effects.
Said Ding, "The advantages of using a single version of the molecule, or enantiomer, are evident: smaller doses, products that are twice as active, fewer side effects, and superior pharmacological profiles of the active compound."
The importance of handedness in drug function extends into every aspect of pharmaceutical development and use, and drug companies are increasing their production of single-enantiomer compounds and their demand for ways to isolate and test only the active form of a drug. The BNL studies can help those companies test such drugs' effectiveness.
Brookhaven National Laboratory carries out basic and applied research in the physical, biomedical and environmental sciences and in selected energy technologies. Brookhaven is operated by Brookhaven Science Associates, a nonprofit research management organization, under contract with the U.S. Department of Energy.