The story

Vittorio Erspamer in Rome spent a career reading frog skin as a chemical library, and it repaid him: he found serotonin's relatives, bombesin, the tachykinins, and then this. In 1980 his group noticed that extracts from Phyllomedusa sauvagei contained something with opioid activity far beyond anything known, and in 1981 Pietro Montecucchi sequenced it and found the D-alanine nobody expected in an animal peptide. Pharmacology followed the same year: 39 times morphine's potency on the gut's opioid receptors, hundreds to thousands of times stronger into the brain fluid, every effect reversed by naloxone, and less tolerance and dependence than morphine produced. The Amazonian tribes of the region had been using the secretion of these frogs for generations under the names Kambo and Sapo, to sharpen themselves as hunters. In 1985 Nicola Basso's group in Italy put it into people properly: 150 patients after surgery, with 20 micrograms placed into the spinal fluid beating 500 micrograms of intrathecal morphine, giving 43 hours of relief against 34, and sending patients home sooner. Then the trail went cold. The 1985 result was never cited by another clinical paper and the molecule was simply forgotten, which two authors revisited in 2018 asking how that could happen in a field desperate for better opioids. The work that continued was largely Russian: Moscow and St Petersburg groups studied its role in mammalian hibernation, mapped how its fragments bind, and in 2025 Vladislav Deigin's group built ring-stabilised analogues that work given into the nose or by mouth, routes the original molecule could never manage.