Derivatives of Drug Also Show Potential To Block Effects of Cocaine
ANAHEIM, Calif., March 22 -- A new more effective form of the drug Ritalin™ (methylphenidate) that produces fewer side effects and has the potential to be used in anticocaine therapy could soon be available, according to research findings presented here today at the national meeting of the American Chemical Society, the world's largest scientific society.
Commonly prescribed to treat Attention Deficit/Hyperactivity Disorder (ADHD), especially in school-age children, Ritalin has an approximate $500 million annual market in the U.S. Estimates vary on the number of youngsters taking the drug, but published reports in the scientific literature indicate that possibly as many as three percent of the country's elementary and secondary students, about 1.5 million, are prescribed Ritalin.
Using a new synthesis developed in his lab, University of Pennsylvania chemist Jeffrey Winkler, Ph.D., and his research group were able to make analogues of Ritalin that he says "have never been prepared before." Additionally, he notes, "Some of those new compounds look like very interesting candidates as anticocaine therapies."
Being able to synthesize "chiral Ritalin" from inexpensive non-chiral starting materials is the key to the drug's improvement, says Winkler. Drug compounds generally have mirror images, known as being right and left handed, but often only one of the "hands" is biologically active, delivering the desired pharmacological agents. Drugs containing "both hands" are called racemic. If a drug can be made one-handed, or chiral, it generally means smaller doses are needed and it avoids any potential side effects that might be contributed from the other hand. Such is the case for Ritalin, says Winkler. "It means less side effects and also less drug would have to be taken," by only including the biologically active right hand of Ritalin. The most common reported side effects of Ritalin are nervousness and insomnia.
Since Ritalin works at the same receptor in the brain as cocaine, Winkler's group is examining their new analogues in cloned cell lines to see if they can be used to block the uptake of cocaine in that area of the brain, without inhibiting the normal flow of dopamine, an important chemical neurotransmitter vital to the proper functioning of the central nervous system.
"We have just developed the most potent compounds known in the literature, which have a ten to one selectivity for inhibiting cocaine without interfering with dopamine," claims Winkler. "And, we have just started our studies," he adds.
While synthesis of the improved form of Ritalin for treatment of ADHD is ready for commercial scale-up, Winkler says, the anticocaine portion of the research is still in the early stages and has yet to be studied in animals and humans.
Lori Krim, a graduate student, will present the paper, ORGN 142, on behalf of Dr. Winkler's research group, on Monday, March 22, at 3:20 p.m., at the Anaheim Hilton, Pacific Ballroom B
A nonprofit organization with a membership of nearly 159,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals and databases, 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.