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Is Ritalin As Effective--And As Harmless--As It Could Be?

Date:
March 31, 1998
Source:
American Chemical Society
Summary:
Ritalin, the treatment of choice for an estimated 2 million or more children suffering from attention deficit hyperactivity disorder, could be more effective and cause fewer side-effects if it were administered as a single compound rather than as a mixture, say chemists at Brookhaven National Laboratory.

DALLAS, March 29 -- Ritalin, the treatment of choice for an estimated 2 million or more children suffering from attention deficit hyperactivity disorder, could be more effective and cause fewer side-effects if it were administered as a single compound rather than as a mixture, say chemists at Brookhaven National Laboratory. Yu-Shin Ding, Ph.D., and colleagues presented their findings here March 29 at the national meeting of the American Chemical Society, world's largest scientific society.

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Methylphenidate (marketed as Ritalin) is a chiral drug, meaning that it comes in two molecular forms, one a mirror image of the other (enantiomers). Currently Ritalin, which topped $350 million in sales last year, said Ding, is distributed as a "racemic" mixture of both its chiral molecules -- d-threo and l-threo.

However, some evidence has suggested that the drug's therapeutic effect resides solely in the d-threo enantiomer, which is about 10 times more potent than its chiral counterpart, according to Ding. "If the beneficial effects of the drug reside only in the d-threo form," she said, "then fifty percent of the weight of the administered drug may not contribute to its therapeutic effects."

Ding, along with colleagues Joanna S. Fowler and Nora Volkow, studied the individual effects of d-threo and l-threo on the central nervous system. They tagged each enantiomer with a short-lived radioactive tracer chemical -- calleda carbon-11 isotope -- with a half-life of 20 minutes. They then used positron emission tomography (PET) to compare the enantiomers' effects in the brains of baboons and humans. (Radiotracers emit signals as they decay that can be collected by a PET scan to generate images.) The study showed that the d-threo enantiomer bound precisely to the dopamine targets in the brain, while the binding of l-threo was mostly non-specific.

What's more, Ding says, the l-threo enantiomer may have some unwanted influence on the active enantiomer or may contribute unwanted side-effects, although long-term human studies would be needed to confirm this. "This leads to the very important issue of whether we should use a racemic drug or a single enantiomer," says Ding. Clincial studies of other drugs, such as the heroin substitute methadone, have shown that single enantiomer forms work best.

Ding and her colleagues say their results illustrate how PET can be used to study the pharmacokinetic properties of chiral drugs. What's more, they say, because of its high-specificity binding of dopamine receptors, d-threo tagged with carbon-11 might prove useful as a PET radiotracer to probe the neuronal loss that occurs in normal aging and in neurodegenerative conditions such as Parkinson's disease.

A nonprofit organization with a membership of more than 155,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.


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The above story is based on materials provided by American Chemical Society. Note: Materials may be edited for content and length.


Cite This Page:

American Chemical Society. "Is Ritalin As Effective--And As Harmless--As It Could Be?." ScienceDaily. ScienceDaily, 31 March 1998. <www.sciencedaily.com/releases/1998/03/980331075111.htm>.
American Chemical Society. (1998, March 31). Is Ritalin As Effective--And As Harmless--As It Could Be?. ScienceDaily. Retrieved January 29, 2015 from www.sciencedaily.com/releases/1998/03/980331075111.htm
American Chemical Society. "Is Ritalin As Effective--And As Harmless--As It Could Be?." ScienceDaily. www.sciencedaily.com/releases/1998/03/980331075111.htm (accessed January 29, 2015).

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