Scientists at New York University have modified the nausea drug netupitant for long-term pain relief to improve its penetration into cells. Research published in the journal PNAS.
The study’s authors focused on two drugs: aprepitant and netupitant. They can block the transmission of pain signals, but they cannot penetrate cells effectively. Scientists genetically engineered mice to express the human NK1 receptor that the drugs target, and then gave them the modified drugs.
The scientists concluded that the active substance is in nanoparticles. Netupitant modification proved to be much more effective in relieving pain in mice. The researchers modified the chemical properties of the drug to improve its ability to cross the cell’s lipid membrane. They have also been modified to stay inside and accumulate when they enter the acidic environment of cell organelles.
Transmission of pain signals takes place inside nerve cells, not on the surface. Therefore, there is a need for drugs that can reach targets within the cell. Such targets are, for example, G protein coupled receptors such as the NK1 receptor. Targeted drugs are used to prevent nausea and vomiting associated with chemotherapy or surgery. Previously, scientists had hoped that the NK1 receptor would be a promising target for pain treatment, but drugs that target the receptor failed to control pain in clinical trials in the 1990s and early 2000s. One reason for the ineffectiveness was that most drugs block receptors on the cell surface.