Ritalin May Work Better as Purer Compound

By Wu, Corinna | Science News, April 4, 1998 | Go to article overview

Ritalin May Work Better as Purer Compound


Wu, Corinna, Science News


Half of every dose of the drug Ritalin, taken by an estimated 2 million children with attention deficit-hyperactivity disorder (ADHD), may contribute nothing to its therapeutic effect, while possibly adding to its side effects, say researchers at Brookhaven National Laboratory in Upton, N.Y.

Ritalin contains equal amounts of two molecular forms, or enantiomers, of the compound methylphenidate. They possess most of the same chemical properties, but structurally they are mirror images of each other. According to the Brookhaven analysis, one enantiomer is much more potent than the other and is responsible for Ritalin's beneficial effects of improving attention and reducing impulsivity.

Yu-Shin Ding, Joanna S. Fowler, and Nora Volkow tested the two forms separately to see how well each binds to receptor molecules in the brain. They labeled methylphenidate with a radioactive tracer, carbon-11, and injected small doses into two volunteers. Using positron emission tomography (PET), the researchers could take images of the brain and see where the drug accumulated.

The scans revealed a "dramatic difference," says Ding. They showed that the form of methylphenidate known as the d-threo enantiomer targets the parts of the brain--the basal ganglia--involved in the drug's therapeutic effect. In contrast, the mirror image l-threo enantiomer distributes itself nonspecifically over the entire brain.

Ding presented the group's findings at a meeting of the American Chemical Society in Dallas this week and proposed using the d-threo enantiomer alone in treating ADHD. The less effective enantiomer may contribute to Ritalin's side effects, including insomnia or loss of appetite, or to longterm complications such as liver damage, speculates Ding. Researchers would need to perform additional studies to determine whether it plays a detrimental role.

Previous studies have indicated that the two enantiomers of methylphenidate cause different behavioral responses in patients, but the Brookhaven study visually establishes where the drug acts in the human brain, says William F. …

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