31 January 2018
The research group led by the colleague of St. Joseph’s Hospital and Medical Center (Phoenix, AZ), professor Andrej Romanovsky, has taken serious steps towards the invention of a brand new painkiller along with the researchers of the University of Pécs, which is free of all side effects.
The discovery of the processes playing part in the development of the pain and the possibilities of easing the pain are currently subject to widespread research. One of the most important starting points of the perception of pain is the pain receptor (newer name: TRPV1 channel) that can be activated in many ways; among its stimuli are the pepper’s “spicy” molecule, the capsaicin, high temperature and acid effects. The activation of the channel causes the perception of pain, its inhibition has proved to be able to ease the pain in several research models and thanks to this, the TRPV1 became an important pharmacological target.
Several world-leading pharmaceutical firms began developing materials inhibiting the TRPV1 channel, so called TRPV1 antagonists. The developments were strongly set back by the fact that in the case of many TRPV1 antagonists a side effect influencing body temperature was discovered, which manifested itself in the forms of low fever, fever or hypothermia. The research group led by Professor Andrej Romanovsky (St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA) – in collaboration with two pharmaceutical firms known globally (AbbVie and Amgen), and with the University of Pécs – set the elimination of this side effect as their goal. This international group consisting of scientific researchers and pharmaceutical developers was the first in the world to demonstrate that the same physiological process is in the background of the different body temperature side effects, thus if we can mitigate the effect regarding this process, the given medicine is not going to influence the body temperature. The results of the research were published in the scientific journal titled Acta Physiologica: http://onlinelibrary.wiley.com/doi/10.1111/apha.13038/full.
In the laboratory of professor Romanovsky they have been examining for more than 10 years the body temperature effects of the TRPV1 antagonists manufactured by different pharmaceutical firms. Dr. András Garami, associate professor at the University of Pécs Medical School Institute for Translational Medicine, and leader of the Thermophysiology Research Group joined this research among the first ones; he is the first author of the freshly published scientific article.
From the University of Pécs, Dr. Erika Pintér (Department of Pharmacology and Pharmacotherapy) and Eszter Pákai (Thermophysiology Research Group) have also participated in the extraordinary discovery. “Up until now we thought that different physiological processes are responsible for the creation of the TRPV1 inhibitors’ body temperature effects. We were surprised that our latest results confuted this and we confirmed that the increase and decrease of body temperature is produced by changing the same physiological process to the opposite directions” – said Dr. András Garami.
Professor Romanovsky added: “The TRPV1 can be activated in several ways but from them only the activation with acid effects is in connection with body temperature. If we obstruct this effect, fever develops, if we enhance it, hypothermia develops.”
This outstanding discovery enables the development of TRPV1 inhibitors free of body temperature side effects since if the newly produced pharmaceutics do not influence the acid activation of TRPV1, the change of the body temperature is not going to evolve either.
“To understand how the pharmacological characteristics of the TRPV1 antagonists are connected with body temperature is particularly important for their usage in a wider circle besides analgesia. Many pharmaceutical firms tried to develop TRPV1 antagonists, moreover, they also conducted initial human studies but because of the undesired body temperature side effect they suspended most of such pharmaceutic developments. The substances produced as a result of the developments were stored, waiting for new utilisation opportunities. For their implementation the thorough understanding of the connection between the pharmacological characteristics and body temperature effect of such a substance provides great assistance, which is namely the result of the research done by Dr. Garami and his colleagues” – said Dr. William Schmidt, chief executive officer of Catalina Pharma.