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    Home > Biochemistry News > Biotechnology News > Nature: Scientists are expected to develop non-opioid analgesics to treat human chronic pain

    Nature: Scientists are expected to develop non-opioid analgesics to treat human chronic pain

    • Last Update: 2021-09-19
    • Source: Internet
    • Author: User
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    The adenosine A1 receptor (A1R) is a very potential therapeutic target for non-opioid analgesics for the treatment of neuropathic pain.
    However, due to the lack of sufficient target selectivity and extra-tissue adverse reactions, analgesic properties The development of positive A1R agonists often faces failure
    .


    Recently, in a research report entitled "Positive allosteric mechanisms of adenosine A1 receptor-mediated analgesia" published in the international journal Nature, scientists from Monash University and other institutions have achieved a major research breakthrough, or development New non-opioid analgesics provide new ideas for safe and effective treatment of neuropathic pain


    Neuropathic pain is a kind of chronic pain.
    If the nervous system of the body is damaged or cannot function normally, this kind of pain will appear.
    It may be caused by injury, viral infection or cancer therapy, or it may be multiple Symptoms or complications of diseases such as sclerosis and diabetes
    .


    In this research report, the researchers proposed a new mode of targeting adenosine A1 receptor protein (A1R).


    Researchers using electrophysiology and preclinical pain models have shown that a special molecule called a positive allosteric modulator (PAM) can provide better results than before by binding to different regions of the protein.
    The traditional activators studied are more selective A1 receptor targets
    .


    Another breakthrough of the research is that the researchers used cryo-electron microscopy technology to solve the high-resolution structure of the A1 receptor, its natural activator adenosine, and an analgesic PAM, thereby providing the atoms bound by these drugs for the first time.


    Chronic pain drugs are still the main health burden of the global population.
    The lack of treatment options at present will lead to excessive dependence on opioid analgesics.
    These drugs have limited relieving effects on chronic pain, especially neuropathic pain, and will also Let patients have serious side effects, such as respiratory depression and addiction
    .


    Researcher Wendy Imlach said that one of the exciting things we found is that PAMs can not only reduce neuropathic pain in patients with minimal unnecessary effects, but they can actually increase with the increase of pain signals in the spinal cord.


    Physiological effects of VCP171 and MIPS521

    Image source: Draper-Joyce,et al.


    In summary, the research in this article provides a new idea and research basis for scientists to develop non-opioid analgesic allosteric drugs based on structure under the background of special diseases


    Note: The original text has been deleted

    Original source:

    Draper-Joyce, CJ, Bhola, R.


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