Dermorphin

Key Benefits#

• Potent analgesia superior to morphine on a per-weight basis
• May reduce perception of fatigue in high-intensity activity
• Longer-lasting than endogenous opioids due to D-amino acid substitution
• Research tool for mu-opioid receptor pharmacology
• Potential therapeutic application in refractory pain

Mechanism of Action#

Dermorphin binds with exceptionally high affinity and selectivity to mu-opioid receptors (MOR), activating Gi/o protein signaling to inhibit adenylyl cyclase, reduce cAMP, and activate GIRK channels. This produces potent analgesia via descending pain inhibition pathways, modulation of spinal nociception, and fatigue-reducing effects via hypothalamic opioid circuits. Its D-amino acid (D-Ala at position 2) confers resistance to enzymatic degradation, extending its duration of action relative to endogenous endorphins.

Dosing Protocols#

Side Effects#

• High addiction and dependence potential (mu-opioid agonism)
• Respiratory depression at high doses
• Nausea, vomiting, constipation
• Sedation and cognitive impairment
• Tolerance development with repeated use
• Prohibited in sport (WADA banned substance)

Contraindications#

No approved human useHistory of opioid use disorderRespiratory compromise or sleep apneaConcurrent opioid medications or CNS depressantsPregnancy and breastfeeding: absolutely contraindicated

Storage#

Lyophilized: store at -20 degrees C. Reconstituted solution: refrigerate at 2-8 degrees C and use within 7-14 days. Protect from light and avoid freeze-thaw cycles.

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   Differential opioid receptor expression and biochemical coupling profiles on glia

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2. 2.
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3. 3.
   Respiratory and Cardiovascular Activity of LENART01, an Analgesic Dermorphin-Ranatensin Hybrid Peptide, in Anesthetized Rats

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5. 5.
   Dermorphin [D-Arg2, Lys4] (1-4) Amide Attenuates Burn Pain by Inhibiting TRPV1/NR2B Mediated Neuroinflammatory Signalling

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10. 10.
    Dermorphin [D-Arg2, Lys4] (1-4) Amide Alleviates Frostbite-Induced Pain by Regulating TRP Channel-Mediated Microglial Activation and Neuroinflammation

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11. 11.
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14. 14.
    Identification of the dermorphin tetrapeptide [Dmt(1) ]-DALDA in a seized unlabelled vial and its first detection in horse urine: A case report

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25. 25.
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29. 29.
    The analgesic hybrid of dermorphin/substance P and analog of enkephalin improve wound healing in streptozotocin-induced diabetic rats

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30. 30.
    The influence of the stereochemistry and C-end chemical modification of dermorphin derivatives on the peptide-phospholipid interactions

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31. 31.
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32. 32.
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33. 33.
    Lesions of the Patch Compartment of Dorsolateral Striatum Disrupt Stimulus-Response Learning

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    A comprehensive approach to detecting multitudinous bioactive peptides in equine plasma and urine using hydrophilic interaction liquid chromatography coupled to high resolution mass spectrometry

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35. 35.
    Dermorphin: A Missed Palliative Care Opportunity for Intrathecal Therapy in Oncological Patients?

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36. 36.
    Rediscovery of old drugs: the forgotten case of dermorphin for postoperative pain and palliation

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40. 40.
    χ-Space Screening of Dermorphin-Based Tetrapeptides through Use of Constrained Arylazepinone and Quinolinone Scaffolds

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    A Blocking Group Scan Using a Spherical Organometallic Complex Identifies an Unprecedented Binding Mode with Potent Activity In Vitro and In Vivo for the Opioid Peptide Dermorphin

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47. 47.
    The impact of β-azido(or 1-piperidinyl)methylamino acids in position 2 or 3 on biological activity and conformation of dermorphin analogues

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48. 48.
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49. 49.
    Characterisation of the Novel Mixed Mu-NOP Peptide Ligand Dermorphin-N/OFQ (DeNo)

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50. 50.
    Cytoprotective Effect of Peptide Sedatin, an Agonist of μ/δ-Opioid Receptors, on Primary Culture of Pulmonary Fibroblasts of Albino Rats under Conditions of Oxidative Stress

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