Dermorphin

What Is Dermorphin?

Dermorphin is a seven-amino-acid peptide (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) originally isolated from the skin of the South American frog Phyllomedusa. It is a highly selective mu-opioid receptor agonist with measured analgesic potency roughly 30 to 40 times that of morphine per unit weight in animal models, and several hundred times morphine when delivered intrathecally. The naturally occurring D-alanine at position 2 confers resistance to peptidase degradation and allows far more efficient blood-brain-barrier penetration than most peptides, which is why microgram quantities are systemically active.

The selectivity for mu over delta and kappa receptors distinguishes it pharmacologically from morphine and most synthetic opioids, but the downstream signalling cascade is the same one that drives the entire opioid class: G-protein-coupled mu-receptor activation, inhibition of adenylate cyclase, hyperpolarisation of pain-relay neurons, and the full opioid effect profile of analgesia, euphoria, sedation, respiratory depression, constipation, tolerance, and physical dependence. There is nothing about its peptide structure that alters this profile. Dermorphin has been detected in racehorse doping cases and is the subject of ongoing interest in opioid-receptor structural biology; it has no clinical development history.