Prolonging the life expectations of patients with progressive cancer could be done by modern medicine. However progressive pain that is associated with progression of disease is the major factor that destructs last moment of life. Severe and progressive and uncontrolled pain is a major reason of requesting euthanasia. The applications of oral (morphine) pills or transdermal patches with lipophylic analgesic drugs are the most common treatments of cancer pain. These compounds penetrating into central nervous system produce side effects (respiratory depression, constipation, tolerance, sedation, etc) to such extend that pain treatment is reduced by the doctor or refused by the patients. The discoveries of the last years indicated the changes in expressions of pro- and antynociceptive receptors in pathologically changed peripheral tissues as well as in central nervous system. The modulation of these receptors with composition of receptor ligands may block nociceptive signal formation and transmission more effectively than traditional monotherapies. The objectives of this project is to focus on development of new multitarget compounds and the method which will interact in large proportion with opioid receptors expressed in inflamed and/or pathologically modified tissues. Partial penetration into central nervous system will results in synergic pain suppression interaction between peripheral and central nervous system. Alternatively, developed compounds could be applied directly into central nervous system to interact with specific, pathological composition of receptors. Developed compounds will be screened in vitro in a cell silicon hybrid biosensor and selected compounds, in vivo in rodent's cancer pain models. Project wills results with new basic data on structural requirements of analgesics for treatment of persistent cancer pain in advances stages and develops new compounds characterized to the stage that allow to promote them for further clinical phase'.
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