methadone-anonymous

Methadone HCL Tablet, Soluble. ... This medication is used to treat addiction to opioids (such as heroin) as part of an approved treatment program. Methadone belongs to a class of drugs known as opioid (narcotic) analgesics.

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Tuesday, December 24, 2019

Methadone Could Be The Most Indicated Non-Addictive Opioid Against Chronic Pain

           One in five people in Europe suffers chronic pain. For its treatment, a new study indicates that it is more appropriate to administer methadone instead of morphine. The results reveal the importance of promoting new therapeutic alternatives that take advantage of the effectiveness of opiates and avoid the side effects derived from tolerance and addiction.PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites."


(Chronic pain responds very well to opioids at first, but in the long term the treatment fails due to tolerance and the risk of addiction)

               Administering methadone instead of morphine is a more appropriate pharmacological treatment in the fight against chronic pain, according to a new article published in the Journal of Clinical Investigation in which experts Vicent Casadó, Estefanía Moreno and Verònica Casadó Anguera, of the Institute, participate of Biomedicine of the University of Barcelona (IBUB) and the Network Biomedical Research Center on Neurodegenerative Diseases (CIBERNED).
              In the work, which describes in molecular models and animals the mechanism of molecular action that produces the therapeutic benefits of methadone, experts from the National Institutes of Health, the University of Maryland and the Massachusetts General Hospital (USA) also participate, among other institutions.
             Addictive substances affect a nervous circuit - the mesolimbic pathway - that is related to the brain's natural reward mechanisms. This mesolimbic reward system is based on dopaminergic neurons of the ventral tegmental area (VTA), which release dopamine in the nucleus accumbens and are responsible for the addictive response to opioids and other compounds.
             Specifically, MOR receptors promote the release of dopamine in the nucleus accumbens and, therefore, participate in both the analgesic and addictive effects of opiates. In contrast, Gal1R receptors counteract the effects of MOR receptors, since they cause a decrease in dopamine release.
             Both the Gal1R receptor and the MOR belong to the family of G-protein coupled receptors (GPCR), the largest group of membrane proteins involved in cell signal transduction and in the control of essential cell functions (neurotransmission, metabolism, proliferation, differentiation, etc.). Therefore, its role is key in many dysfunctions related to pathologies and in the physiological response to drugs.
            In addition, it has been shown that the ability to form dimers between GPCR receptors (homodimers or heterodimers) is associated with the acquisition of new pharmacological and functional properties different from those of their individual components, a condition that allows finer control of their physiological functions. 
            In this context, designing drugs that interact with these oligomeric complexes of some receptors - with a specific location - involved in a specific pathology would allow for new strategies to reduce side effects and improve the effectiveness of pharmacological treatments.
            Methadone versus Morphine
           According to the new work, in the murine models studied a high percentage of the Gal1R and MOR receptors form MOR-Gal1R heteromers in the ventral tegmental area (but not in the spinal cord).PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites."
Image result for Por lo tanto, los efectos generados por la activación de los receptores MOR del área tegmental ventral –que forman heterómeros con los receptores Gal1R– podrían contrarrestarse mediante la coadministración de ligandos de Gal1R con opiáceos.

          Since methadone acts preferentially on MOR receptors when they do not form heteromers with Gal1Rs, their effect is mainly peripheral. For this reason, methadone's ability to activate the dopaminergic system is lower compared to morphine and fentanyl, which can act interchangeably on MOR receptors or on MOR-Gal1R complexes. This would explain the greater proportion of analgesic effects of methadone administration, a substance that could be profiled as the most appropriate non-addictive opioid to treat chronic pain.
(The work describes in cellular and animal models the mechanism of molecular action that produces the therapeutic benefits of methadone)
         According to experts, the ability to form heteromers could also be used as a new therapeutic strategy to counteract the addictive dopamine effects of opiates. It should be remembered that, in previous work, the team had already shown that galanin - neuropeptide with neurotrophic and neuroprotective properties - is capable of causing a decrease in the release of dopamine in the nucleus accumbens.PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites."
        Therefore, the effects generated by the activation of the MOR receptors of the ventral tegmental area - which form heteromers with the Gal1R receptors - could be counteracted by co-administration of Gal1R ligands with opiates.




         




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