Inhibition of Glycine Transporter 2: An Emerging Target for Chronic Pain
Chronic pain is a complicated, completely unknown condition that has been studied based on its severe impact on the population. According to the American Academy of Pain Medicine, 1.5 billion people suffer from tension-type headaches, one of the most common symptomatic chronic conditions. Christopher L. Cioffi, 2019; mentioned approximately in US 116 million adults are explicitly afflicted by chronic pain. Chronic pain is described as dysfunction in nerves that have been continuous during a long period (Mills, 2019). Treatments for chronic pain are different types of common analgesics that relieve the pain for short periods such as aspirin, ibuprofen, paracetamol, etc. (Hunging, 2017) Accord to the level of it, such as opioids, anticonvulsants drugs, antidepressants, and anti-inflammatory drugs are some of the treatments used for severe pain. One of the most common therapies is opioids, as relievers of pain available legally by prescription. Opioids are considered one of the most effective drugs for the treatment of several levels of pain (Wood, 2019). In most of the world, opioids have been the solution to controlling severe or constant pain, such as chronic pain. The several side effects that opioids produce create several concerns related to patient safety and abuse addiction. (Rosenblum, Marsch, Joseph, & Portenoy, 2008) Secondary side effects that do not let opioids be a correct option for chronic pain treatment are diverse; for example, the high rate of addiction or possible drug abuse (Edlund, 2007). "Injury to the somatosensory system (neuropathic pain), degenerative processes and chronic inflammation (i.e., osteoarthritis and rheumatoid arthritis), disease (i.e., cancer pain)" (Cioffi, 2019) are some of the suggested risks or suffer chronic pain and the analgesic resistance that patients development through their fight with the problem makes harder to avoid the use of opioids. Therefore, several research types are interested in finding new therapies that avoid the use of opioids—looking for better options to find relief for those patients who continuously are suffering from pain. The virtual screening method developed achieved a high hit rate of 75%. By analyzing more and more new compounds and looking for possible chronic pain treatment targets, the discovery of a group of new compounds with good inhibitory properties and selectivity it seems to be possible. Hit1 is considered to be the first and main candidate for further optimization of potential customers and detailed, more specific analysis of the ligand. We observed that some of the factors that make Hit1 the main ligand, such as the stable hydrogen bond that interacts with glycine transporter 2, showed a development similar to ALX1393 activity. Through several MD simulations. The results provided a structural basis for the Hit1 selectivity observed experimentally in GlyT2. The result displayed by Hit2 is closest to Hit1. The inhibition of glycine transporters, especially glycine transporter 2 (GlyT2), has been shown promise for new treatments for chronic pain based on their role in the neurotransmission of pain signals. They are improving the knowledge in better ways to find cures for chronic pain with fewer consequences in the process.
Padilla Mendez, Elvia Lilia, "Inhibition of Glycine Transporter 2: An Emerging Target for Chronic Pain" (2020). ETD Collection for University of Texas, El Paso. AAI28261897.