Introduction
In 1979, GOLDSTEIN et al. extracted an opioid-active 17 peptide from the pituitary of pigs and named it dynorphin. Dynorphin, as one of the endogenous opioid peptides, is also an important class of neurotransmitters with extensive functions, especially in the regulation of pain. Dynorphin (1-17) is a dynorphin consisting of fragment structures 1-17 and is one of the major active fragments in the dynorphin family with the best analgesic effect.
Pharmacologic action
Dynorphin (1-17) is closely related to ion channels on the cell membrane. When the nociceptive nerve is excited, the body releases the dynorphin and transports it around the synapse, activating the k receptor. When the k receptor is activated, it inhibits the activation of K+ or Na+ channels, delays the repolarization of the cell membrane, and prolongs the action potential to regulate pain sensitivity. On the other hand, through the G protein coupling mechanism, it inhibits cyclic adenosine monophosphate (cAMP), inhibits calcium influx, and reduces the release of a series of pain media such as substance P, thereby exerting an analgesic effect. In addition, dynorphin (1-17) can alter the sensitivity of pain-induced afferent fibers C and Aδ to pain stimuli, resulting in an analgesic effect.
Function
The opioid effect of dynorphin is 190 times stronger than normorphine and 700 times stronger than leu-enkephalin. Injecting dynorphin into the subarachnoid space of the spinal cord presents a strong and long-lasting analgesic effect. According to the analgesic score, the analgesic effect is 6-10 times stronger than morphine. Studies have shown that intrathecal injection of anti-dynorphin after spinal cord injury can reduce heat-irritating pain and mechanical pain, but it cannot alleviate formalin-induced inflammatory pain, indicating that the effect of dynorphin analgesia depends on the form of pain. In addition, the effect of dynorphin is also affected by the site of action, the type of receptor acting, and even the type of neuron released
Pharmacokinetics and metabolism
Dynorphin (1-17) has high fat solubility, short biological half-life, small apparent volume distribution, rapid distribution, and can quickly reach the peak through the blood-brain barrier after administration. The main metabolite of dynorphin (1-17) is formed by hydrolysis of peptide bonds, mainly Dyn (1-6), Dyn (1-8), Dyn (1-13) and Dyn (2-17). It is mainly excreted by the liver and kidneys.
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