Novel medicine to fight addiction has been developed, which could also be effective in treating epilepsy and other conditions, reveals a new study.
Drug addiction continues to plague vast numbers of people across the world, destroying and ending lives, while attempts to develop more effective pharmaceutical addiction treatments continue.
Scientists have reported the findings of this study in the Journal of the American Chemical Society.
In humans, vigabatrin eliminates cocaine addiction in 28 percent of patients. It works by blocking an enzyme, γ-aminobutyric acid (GABA) aminotransferase, which breaks down GABA.
The result is higher levels of this neurotransmitter in the brain and diminished narcotic-activated release of dopamine.
Long-term vigabatrin therapy can have serious side effects however, causing eye damage in up to 40 percent of those treated. So, Richard B. Silverman, Stephen L. Dewey and colleagues wanted to develop a more potent inhibitor of GABA aminotransferase with fewer side effects.
In previous work, the researchers designed a compound, CPP-115, that is 186 times more efficient in inactivating GABA aminotransferase than vigabatrin.
In this study, they used computational molecular dynamics simulations of CPP-115 in complex with the enzyme to develop a new and improved agent with 10 times greater efficiency.
The drug should also be less likely to cause side effects, as it has fewer off-target activities in in vitro tests.
In initial rat experiments, the new compound was far better at blocking dopamine release after a cocaine or nicotine stimulus than CPP-115.
The researchers say that future work could examine whether the computational approach could be generalized to improve other mechanism-based enzyme inhibitors in the laboratory before testing them on animals.