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A New Non-Addictive Pain-relieving Drug

Scientists have discovered a safe and non-addictive synthetic bifunctional drug for relieving pain


Opioids provide the most effective pain relief. However, opioid usage has reached a crisis point and is becoming a huge public health burden in many countries especially in USA, Canada and United Kingdom. The ‘opioid crisis’ began in the 90s when physicians started prescribing opioid-based pain relievers like hydrocodone, oxycodone, morphine, fentanyl, and several others at a higher rate. As a consequence, prescribed number of opioids are currently at peak levels leading to high consumption, overdose and opioid abuse disorders. Drug overdose is the leading cause of death in younger people who are otherwise disease-free. These drugs are highly addictive as they are accompanied by feelings of euphoria. The most common prescription opioid drugs like fentanyl and oxycodone also produce many undesired side effects.

Scientists have been looking to find an alternative painkilling drug which would be as effective as opioids in relieving pain but minus unnecessary dangerous side effects and risk of addiction. The central challenge of finding an alternative has been that opioids work by binding to a group of receptors in the brain which simultaneously block pain and also trigger feelings of pleasure which causes addiction. In a breakthrough study published in Science Translational Medicine, scientists from USA and Japan set out to develop a chemical compound which will focus on two targets i.e. two specific opioid receptors in the brain. The first target is the “mu” opioid receptor (MOP) which traditional drugs bind to, making opioids so effective in relieving pain. The second target is nociception receptor (NOP) which blocks addiction and abuse related side effects of opioids which target MOP. All prescription opioid drugs known work only on the first target MOP and that it why they are addictive and also show a range of side effects. If a drug can work on both these targets simultaneously that would solve the problem. The team has discovered a novel chemical compound AT-121, which exhibits the required double therapeutic action, in an animal model of non-human primates or rhesus monkeys (Macaca mulatta). The study was conducted on 15 adult male and female rhesus monkeys. AT-121 suppresses addictive effects while producing morphine-like analgesic outcome for treatment of pain. The effect is similar to what the compound buprenorphine does for drug heroin. The lower risk of addiction was adjudged by a simple experiment in which the monkeys were given access to self-administer AT-121 by pressing a button, and they chose not to do so. This was in stark contrast to oxycodone, a conventional opioid drug, which the animals would keep administering until they had to be stopped from overdosing. Thus, in this short-term experiment, monkeys did not show any signs of addiction.

Pharmaceutically, AT-121 is a balanced combination of two drugs in a single molecule and thus is being called a bifunctional drug. AT-121 exhibited similar level of effective respite from pain as morphine, but at a dosage hundred-fold lower than morphine. This is an innovative discovery as this medicine was able to relieve pain without risk of addiction and also minus the harmful side-effects which are commonly seen with opioid overdose such as itching and fatal respiratory effects. Similar studies were earlier conducted on mice; however, medicines did relieve pain effectively but they were still addictive and thus were not considered suitable alternatives to existing opioid painkillers.

The current study was conducted in a primate model (monkeys) - a closely related species to humans - making this study more promising with higher probability of similar results in humans. Therefore, compound like AT-121 is a potential viable opioid alternative. Scientists look to conduct further pre-clinical trials to ensure safety of AT-121 before evaluating it in humans. The drug also needs to be tested for ‘off-target activity’ i.e. any possible interaction it makes with other areas on the brain or even outside the brain. This will help to determine any other likely side effects. The drug shows huge promise as a safe alternative medication for treating pain. If successfully tested on humans, it can help to placate medical burden by making a huge impact on human lives.


Huiping Ding et al. 2018, ‘A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates', Science Translational Medicine, Vol. 10, no.456,

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Vol.1 Issue 9 September 2018