51ºÚÁϳԹÏÍø

Abstract

Opioids are the main endogenous system, which is significantly involved in the modulation of pain signaling pathways and its perception. That is why to this day opioids occupy a strong position in the treatment of various pain conditions. However - apart from the desired analgesia - their administration is associated with a wide variety of side effects, such as nausea, vomiting, and respiratory failure. Critics also point out a specific risk of the development of analgesic tolerance to and dependence on these drugs. One of the solutions to this problem is hybrid (chimera), in which part of the opioid is hybridized with different type of synergistically/adjuvantly acting compound, such as neurotensin (NT). This naturally existing peptide is characterized by the fact that its central application resulted in strong analgesic response independent of the activation of the opioid system. Hence, by a chemical bounding of opioid with neurotensin, the active analgesic compound is obtained which is characterized by its presumed safety profile. Here in novel hybrid compounds containing both opioid and neurotensin pharmacophores will be presented. High antinociceptive effects of investigated peptides were proven by comparing their potency with morphine injected at 150-time fold higher dose. These results give hope that more efficient opioid analgesics are accessible through the combination of the agonism at opioid and NT receptors.

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