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Adding Vitamin C To Certain Drugs May Help Treat Alzheimer's, Other Brain Disorders

Date:
January 11, 2002
Source:
American Chemical Society
Summary:
Drugs used to treat Alzheimer’s and other brain disorders appear to enter the brain more easily when a vitamin C molecule is attached, according to researchers in Italy. The discovery could lead to safer and more effective drugs that target the brain, they say.

Drugs used to treat Alzheimer’s and other brain disorders appear to enter the brain more easily when a vitamin C molecule is attached, according to researchers in Italy. The discovery could lead to safer and more effective drugs that target the brain, they say.

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The study is tentatively scheduled to appear in the Jan. 31 print issue of the Journal of Medicinal Chemistry, a peer-reviewed publication of the American Chemical Society, the world’s largest scientific society. It was published in the Web edition of the journal on Dec. 21.

“We’ve opened a door for a promising new way to improve delivery of drugs into the brain using a natural nutrient, ascorbic acid [vitamin C],” says Stefano Manfredini, lead investigator in the study and a professor of pharmaceutical chemistry at the University of Ferrara in Ferrara, Italy.

Some drugs that have difficulty entering the brain could cross more easily when attached to a vitamin C molecule, while some that cannot enter the brain could enter for the first time, he says. Potential applications include drugs for central nervous system diseases, viral infections (including AIDS), brain lesions, and neurodegenerative diseases including Alzheimer’s, Parkinson’s and epilepsy, Manfredini says.

He calls the results “exciting,” but cautions that the data are very preliminary. So far, animal tests of at least one of the vitamin C modified drugs appear promising, but no human tests have been conducted. The new design approach will not enhance the effectiveness of all drugs, while those that do work could take several years to reach the consumer market, the researcher predicts.

One of the major problems in the treatment of brain diseases is the difficulty of distributing drugs to the central nervous system. This is due to a natural barrier, the blood brain barrier, which selectively regulates the movement of chemicals across the brain.

Researchers have known for some time that adding new components to drugs may improve their ability to cross this barrier. For example, glucose and amino acid units have allowed improved penetration into the blood brain barrier for some drugs, according to researchers.

Researchers recently discovered the existence in some cells of a new receptor, the SVCT2 transporter, which is believed to play a major role in regulating the transport of vitamin C into the brain, where vitamin C is found at high concentrations. Manfredini and his associates theorized that adding a vitamin C component to certain therapeutic drugs would facilitate their transport across these receptors and their entry into the brain.

To test their theory, the researchers studied three different compounds that are used to treat brain disorders — ranging from epilepsy to Alzheimer’s — but are known to have difficulty crossing the blood brain barrier. Those compounds are nipecotic acid, kynurenic acid and diclofenamic acid. Researchers tested the compounds in the laboratory using human retinal pigment epithelial cells, which are rich in vitamin C transporters. This laboratory model has the same SVCT2 transporter as the blood brain barrier, allowing researchers to predict drug transport across the blood brain barrier in humans, they say.

Adding a vitamin C component to each of these three compounds significantly improved their ability to interact with the vitamin C transporter. While nipecotic and kynurenic acids normally cannot interact with the transporter, the same drugs with a vitamin C component added can interact. Although diclophenamic acid normally blocks the vitamin C transport, the same drug with a vitamin C component interacts with the transporter without blocking vitamin C. The results suggest that this approach may improve drug delivery in actual living organisms, the researchers say.

To test the effect of a modified drug in an animal model, the researchers chose nipecotic acid, which cannot easily enter the blood brain barrier in its normal form. Using a group of mice that had been chemically induced to have convulsions, the researchers injected the normal molecule into the mice. This had no effect on their convulsions. When a vitamin C modified version of the drug was injected, convulsions were delayed, demonstrating the improved performance of the drug, the researchers say.

Side effects in the mice were very limited and no deaths were reported, they say.

Additional animal studies of vitamin C modified drugs are anticipated, Manfredini and his associates say. They have filed a patent for their discovery.

The researchers also believe that the in vitro cell model of vitamin C transporters used in this study will serve as a valuable tool to study one of the many mechanisms by which ascorbic acid works in the body, a mystery scientists have yet to fully understand. An understanding of these mechanisms could provide insights into many of the controversial health claims regarding vitamin C, they say.

The university and the National Institutes of Health provided funding for this study.


Story Source:

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. "Adding Vitamin C To Certain Drugs May Help Treat Alzheimer's, Other Brain Disorders." ScienceDaily. ScienceDaily, 11 January 2002. <www.sciencedaily.com/releases/2002/01/020110075058.htm>.
American Chemical Society. (2002, January 11). Adding Vitamin C To Certain Drugs May Help Treat Alzheimer's, Other Brain Disorders. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2002/01/020110075058.htm
American Chemical Society. "Adding Vitamin C To Certain Drugs May Help Treat Alzheimer's, Other Brain Disorders." ScienceDaily. www.sciencedaily.com/releases/2002/01/020110075058.htm (accessed November 23, 2014).

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