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All opioid drugs from poppy-derived opium to heroin work on receptors that are naturally present in the brain and elsewhere in the body. One such receptor, the mu-opioid receptor, binds to natural pain-killers in the body called endogenous endorphins and enkephalins. Drugs acting on the mu-opioid receptor can cause addiction as well as unwanted side effects like drowsiness, problems with breathing, constipation and nausea. "Normally, when you are in pain, you are releasing endogenous opioids, but they're just not strong enough or long lasting enough," says Traynor. The team had long hypothesized that substances called positive allosteric modulators could be used to enhance the body's own endorphins and enkephalins. Oxycodone binds to so-called opioid receptors in the body. There are three different types: MOP, DOP and KOP. The painkillers available to date mainly activate the MOP (also called ?-opioid receptor). However, stimulating MOP can not only be addictive, it can also have life-threatening side effects. The most serious is respiratory paralysis, which is why the most common cause of death after heroin use is respiratory arrest. "Drugs that selectively bind to the DOP receptor probably do not have these dramatic side effects," hopes Prof. Dr. Christa Müller from the Pharmaceutical Institute at the University of Bonn. The emphasis is on "selective": The opioid receptors are so similar that many drugs activate all three forms. In order to find substances that only dock to the DOP receptor, it is therefore necessary to know exactly what happens during the binding process. Spatial structure made visible down to the atomic level The current study can now answer this question. "We have activated the DOP receptor with two different molecules, purified the complex and then elucidated its structure using X-rays," explains Tobias Claff, who carried out the majority of the experiments. For this purpose, the complex of receptor and active substance is transformed into a crystalline state. The crystal lattice deflects the X-ray light in a characteristic manner. The intensity distribution of the diffracted radiation can therefore be used to deduce the spatial structure of the complex, right down to the arrangement of each individual atom.