We are talking about a mixture of two recently developed drugs – Rapablock and Rapalink-1 – that affect the mTORC1 protein complex, Nature Communications reports.
American scientists have found that alcohol addiction can be blunted with a combination of two drugs that inhibits the work of “alcoholism proteins” in brain cells, but not in other body tissues. The results of experiments on mice were presented in an article in the journal Nature Communications.
“The mTORC1 protein, which is affected by these drugs, has long been associated with the development of various forms of drug addiction. This gives hope that the combination of Rapablock and Rapalink-1 drugs can be used not only for the treatment of alcoholism but also for other forms of addiction,” the researchers write.
Over the past decade, neurophysiologists and geneticists have discovered that alcoholism and other forms of addiction arise as a result of the development of disorders in the work of certain types of nerve cells present in the nucleus accumbens of the brain and some of its other areas associated with the work of the sense of pleasure. These discoveries force biologists to look for substances that restore the work of these neurons and make them ignore alcohol.
A group of biologists led by Dorita Ron, a professor at the University of California at San Francisco, discovered that a mixture of two recently developed drugs-Rapablock and Rapalink – 1-acting on the mTORC1 protein complex has similar properties.
It is a complex structure of several enzymes that control the metabolism and synthesis of proteins in cells and are responsible for responding to a shortage or influx of nutrients and oxygen. Violations in the work of mTORC1, as scientists ‘ observations show, lead to failures in the immune system and also increase the likelihood of developing cancer, diabetes, and some other diseases.
Suppression of addiction
Recently, scientists have discovered that the activity of this protein complex increases dramatically in those nerve cells of mice and alcoholic people that are directly associated with the development of addiction. The first experiments indicated that the suppression of mTORC1 significantly reduces the craving for alcohol among animals, but this procedure led to the development of serious problems with the liver.
Professor Ron and her colleagues tried to circumvent this problem by using a combination of Rapalink-1 and Rapablock drugs that affect the body in the opposite way. The first substance suppresses the activity of mTORC1 proteins, while the second prevents it from doing this. At the same time, Rapalink-1 can penetrate the barrier separating the brain from the circulatory system, whereas Rapablock is not able to do this.
For this reason, simultaneous administration of Rapablock and Rapalink-1 leads to the fact that the work of mTORC1 is blocked only in brain cells, while this protein complex continues to function in the liver and other parts of the body. Guided by similar considerations, biologists tracked how the combination of these drugs would affect the behavior and health of mice suffering from alcoholism.
As subsequent observations showed, the combination of these substances sharply reduced the mice’s interest in alcohol and forced them to consume about 2-3 times less ethanol than they did before taking the drugs. At the same time, the rodents did not suffer from the characteristic side effects associated with the suppression of the work of mTORC1 in the cells of the liver and other organs of the body.
Shortly, scientists plan to test whether it is possible to suppress other bad habits in this way, and will also study how safe long-term use of Rapablock and Rapalink-1 will be. The researchers hope that these experiments will open the way for clinical trials of these drugs on volunteers.