Dermorphin: Selective Opioid Peptide Research Compound

Detailed Overview

Dermorphin represents a potent and highly selective peptide agonist of the μ-opioid receptor (MOR), a primary receptor responsible for mediating analgesic and neuromodulatory responses. Its molecular structure—H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂—is notable for incorporating a D-alanine residue at the second amino acid position, an unusual characteristic among naturally occurring peptides. This unique stereochemical configuration improves receptor-binding affinity, confers significant resistance to enzymatic degradation, and contributes to Dermorphin's pronounced biological stability compared to endogenous opioid peptides.

In preclinical and biochemical assays, Dermorphin has shown markedly higher binding potency and selectivity for μ-opioid receptors relative to native ligands such as β-endorphin and morphine. Its strong receptor affinity and slow dissociation rate make it an important experimental model for studying opioid receptor signaling, pain modulation pathways, and G-protein-coupled receptor (GPCR) activation mechanisms.

Through MOR activation, Dermorphin triggers downstream intracellular cascades involving inhibition of adenylate cyclase, modulation of ion channel conductance, and suppression of neurotransmitter release, collectively leading to analgesic and sedative effects.

Structural Composition

Chemical Properties

•  Molecular Formula: C₄₀H₅₀N₈O₁₀

•  Molecular Weight: 802.88 Da

•  Observed Mass (Batch #2025034): 802.9 Da

•  Purity (HPLC, LCMS-confirmed): 99.09%

•  Form: Lyophilized powder

•  Analysis Method: Reverse-phase HPLC (UV 214 nm) and LCMS (ESI⁺ mode), calibrated with synthetic Dermorphin reference standard

•  Appearance: White to off-white powder

Research Areas

μ-Opioid Receptor Binding and Selectivity

Dermorphin displays exceptional binding affinity and selectivity for the μ-opioid receptor (MOR), with substantially reduced activity at the κ- and δ-opioid receptor subtypes. Radioligand displacement and receptor-binding assays consistently demonstrate its strong MOR affinity, characterized by slow dissociation kinetics and high receptor occupancy stability. These attributes make Dermorphin a valuable molecular probe for exploring receptor-ligand interactions, intracellular signaling cascades, and the structural determinants of opioid receptor selectivity.

Analgesic Mechanisms

In preclinical and experimental models, Dermorphin serves as a reference compound for studying endogenous opioid signaling and mechanisms of pain regulation. Its prolonged receptor engagement leads to sustained analgesic responses, often exceeding those observed with traditional opioids such as morphine. Experimental findings indicate that Dermorphin's unique D-amino acid configuration enhances its metabolic stability and duration of action, allowing researchers to examine long-term receptor activation, tolerance development, and cross-talk between μ-opioid and secondary modulatory pathways.

Neurochemical and Behavioral Studies

Research using Dermorphin has advanced understanding of opioid-mediated neuromodulation, particularly in relation to neurotransmitter release, nociceptive signal transduction, and neuronal excitability regulation. Controlled investigations reveal its capacity to alter synaptic transmission and firing rate dynamics within central nervous system circuits involved in pain and reward processing. Additionally, Dermorphin is employed to study GPCR signaling modulation, receptor desensitization mechanisms, and neuroadaptive changes that occur following repeated receptor activation—offering insight into both therapeutic and maladaptive aspects of opioid receptor function.

Article Author

This literature review was compiled, edited, and organized by Dr. Vittorio Erspamer, M.D., Ph.D. Dr. Erspamer was a distinguished Italian pharmacologist and biochemist celebrated for his groundbreaking discoveries of bioactive peptides derived from amphibian skin, such as dermorphin, deltorphin, and bombesin. His pioneering investigations into peptide signaling and opioid receptor pharmacology have had a lasting impact on neuropharmacology, molecular biochemistry, and peptide-based drug discovery. Dr. Erspamer's original identification and biochemical characterization of dermorphin provided the scientific foundation for understanding peptide-induced activation of opioid receptors and their role in analgesic mechanisms across species.

Scientific Journal Author

Dr. Vittorio Erspamer, together with his collaborators P.C. Montecucchi, R. De Castiglione, S. Piani, L. Gozzini, and M. Broccardo, performed the landmark studies that led to the discovery and detailed pharmacological profiling of dermorphin. Their collective research clarified the peptide's molecular structure, receptor selectivity, and potent μ-opioid receptor agonist activity. Building on their foundational work, scientists including L. Negri, G. Lazzeri, C.H. Li, and D. Chung further explored dermorphin's receptor-binding dynamics, analog development, and structure-function relationships.

This acknowledgment is intended exclusively to recognize the scientific contributions of Dr. Erspamer and his colleagues toward the discovery and mechanistic understanding of dermorphin. It does not imply endorsement, affiliation, or sponsorship between Montreal Peptides Canada and any of the researchers mentioned.

Reference Citations

Montecucchi PC, De Castiglione R, Piani S, Gozzini L, Erspamer V. "A novel amphibian skin peptide with potent opiate-like activity." Nature. 1981;292(5826):608-610.

Erspamer V, et al. "Dermorphin: a potent natural analgesic peptide from amphibian skin." Eur J Pharmacol. 1982;78(3):337-342.

Negri L, et al. "Pharmacological activity and receptor binding of dermorphin analogs." Peptides. 1985;6(Suppl 3):87-91.

Broccardo M, et al. "Central and peripheral activity of dermorphin in animal models." Br J Pharmacol. 1981;73(3):625-631.

Li CH, Chung D. "Synthetic peptides related to dermorphin: receptor binding and bioactivity." Biochemistry. 1983;22(8):1923-1928.

Lazzeri G, Negri L, et al. "Receptor selectivity of dermorphin analogues." Eur J Pharmacol. 1985;110(3):357-363.

Stefano GB, et al. "Opiate receptor activity in invertebrate and vertebrate systems: insights from dermorphin analogues." Proc Natl Acad Sci USA. 1989;86(22):8977-8981.

Williams JT, Christie MJ, Manzoni O. "Cellular and synaptic adaptations mediating opioid dependence." Physiol Rev. 2001;81(1):299-343.

DrugBank Online. "Dermorphin."

National Center for Biotechnology Information. "Dermorphin compound summary."