Function of DAMME in analgesia
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Function of DAMME in analgesia



DAMME (DA) is a guanine, often referred to as FK 33-824 (FK), which is a long-acting enkephalin analog. Natural enkephalin is metabolized faster in the body and can only exert weak and transient analgesic effects. The synthetic enkephalin analog DAMME is less sensitive to metabolic breakdown and can be present in the body for a long time, so it has a long-lasting and effective analgesic effect on animals after systemic and enteral administration. It has an analgesic effect on inflammatory pain, neuropathic pain and cancer pain. Therefore, it has a good prospect in the field of analgesia.

Pharmacologic action

DA participates in the endogenous pain modulation system through the μ receptor and the δ receptor, and exerts an analgesic function. It inhibits the activation of K + or Na + channels with its receptor junction, delays the repolarization of the cell membrane, and prolongs the action potential that regulates 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.


It has been reported that the application of trace amounts of DA in the rat brain can produce significant analgesic effects, while large doses (10 mg) of intrathecal administration do not cause significant respiratory and circulatory disorders. In a double-blind study, intramuscular administration of 0.25 mg DA significantly increased tolerance without affecting the pain threshold. Due to its vasodilatation, using 50 mg of beta-azole as a "placebo", 1.0 mg DA significantly increased pain tolerance by more than 0.25 mg DA, while the threshold remained unchanged. Therefore, 1.0 mg DA i.m can increase tolerance rather than pain, mimicking the analgesic effect of morphine.

Pharmacokinetics and metabolism

DA has a longer half-life than enkephalin. 60% of DA in brain tissue is not destroyed by enzymatic hydrolysis within 30 min and can effectively cross the blood-brain barrier. After intramuscular injection of DA, the heart rate, pulse, respiration and body temperature of the human body have no relevant changes within six hours, but there is a feeling of muscle heaviness, which will disappear within 15-30 minutes. DA belongs to peptides and is finally hydrolyzed in the liver without hydrolysates and metabolites.


Beat Von Graffenried, Emilio Del Pozo, Jiri Roubicek, Eva Krebs, Walter Pöldinger, Peter Burmeister, et al. Effect of the synthetic enkephalin analogue FK33-824 in man[J]. Nature, 1978, 272(5655), 729-730.

Gonzalez NV, Gonzalez AJ, Barreto VK, et al. In vivo regulation of the μ opioid receptor, role of the endogenous opioid agents[J]. Molecular medicine,2013, 19, 7-17.

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