Emory Report

 November 10, 1997

 Volume 50, No. 12

Yerkes studies reveal new medications for addiction

Researchers at the Yerkes Primate Center have synthesized a compound that shows promise for people addicted to cocaine and amphetamines. Currently there is no treatment to help the millions of Americans who abuse these drugs.

These and other studies by Yerkes scientists describing the neural pathways involved in cocaine addiction were presented at the annual meeting of the Society for Neuroscience in New Orleans.

Chemical compound similiar to cocaine
A new chemical candidate for treating cocaine addiction, called RTI-113, is similar in structure to cocaine. It is one of a new class of compounds called phenyltropanes, which alter the same brain systems targeted by cocaine and related drugs but are thought to have a lower abuse liability and minimal side effects and toxicity. Once in the brain, RTI-113 selects and binds successfully to the same dopamine transporters that cocaine targets. It is potent, yet it enters the brain more slowly than cocaine. Most addictive drugs have a rapid entry to the brain, accounting for the "rush" felt by users. RTI-113 is also long-lasting, which facilitates an easy dosing schedule in a treatment setting.

In monkeys, RTI-113 substitutes completely for cocaine, resulting in a reduction in the monkeys' cocaine self-administration, which is the best model of drug-seeking and drug-taking behavior in humans.

In people, the medication would be taken orally to relieve craving for cocaine and thus help manage the urge for "out-of-control," illegal and destructive drug-seeking behaviors. "This type of therapy is a critical first step in getting an addict off cocaine and into a treatment and social support program," said Mike Kuhar, chief of Yerkes' neuroscience division. "It is not a cure but a major step in reducing drug use and its enormous cost to society in terms of physical and mental health, crime and safety."

The goal, he said, is to develop a medication that can be controlled and dispensed by a treatment center physician and will act as a safe steppingstone in the process of withdrawal. It would provide the addict and the treatment center staff the control needed to set in place a detoxification program. Many addicts leave treatment because of the persistent, demoralizing urge to find drugs. "A medication to break this cycle is essential," said Kuhar.

Kuhar and his colleagues, particularly Ivy Carroll, a medicinal chemist, began synthesizing phenyltropanes 10 years ago. From nearly 500 compounds, they have narrowed the field to about 25 candidates for further testing.

Because compounds cannot be tested in humans unless they are proven likely to be safe and effective, rat or monkey models are used. In the self-administration model, an animal is given the opportunity to obtain an injection of a drug by pressing a lever. If the animal likes the drug, it will press the lever again and again. However, the animals are permitted access to the drug only in very short intervals to avoid toxic effects and are closely monitored.

-Kate Egan

Return to November 10, 1997 Contents Page