How opioid drugs get into our cells

Activation of opioid receptors inside a cell. UNIGE - Miriam Stoeber Unlike natural opioids, opioid drugs penetrate our cells, which explains both their high efficacy and their side effects, reveals a team from the University of Geneva. The human body naturally produces opioid-like substances, such as endorphins, which block the perception of pain and increase the feeling of well-being. Similarly, opioid drugs, including morphine or fentanyl, are widely used for alleviating severe pain. However, their use is associated with a high risk of dependence and addiction, and their excessive misuse causes over 350,000 annual deaths worldwide. Researchers from the University of Geneva have compared the action of natural and therapeutic opioids. The latter penetrate inside the cells to activate opioid receptors, whereas natural opioids are unable to enter cells and activate only receptors located on the cell surface. The location of the activated receptors could therefore explain why opioid drugs trigger very different physiological responses from those induced by natural opioids. The results, to read in Science Advances , could help to develop safer and more effective medications that better mimic natural opioids. Opioids consist of a broad group of painkiller drugs, highly powerful but with potentially severe side-effects. The human organism's response to these medications is governed by opioid receptors that belong to a large family of membrane receptors called GPCRs, which are present in all our cells and mediate a wide range of physiological functions, from vision and smell to brain function. Opioid drugs activate these receptors in neurons, thereby inducing signals that block the sensation of pain. But why do the effects of different opioids vary?