The repurposing of old drugs for new indications is becoming more accepted as a cost-efficient
solution for complicated health problems. However, older drugs are often forgotten when they are not repositioned. This analysis makes a case for re-exploration of
dermorphin for intrathecal use in
postoperative pain and in a palliative context, with the goal of re-establishing this compound.
Dermorphin was isolated from the skin of an Amazonian frog, characterized and identified as a bioactive heptapeptide by Vittorio Erspamer's research group in the early 1980s. It was traditionally called "Kambo" or "Sapo" by Amazon tribes and was used to improve their physical and psychic skills as hunters. Its structure is rather enigmatic, containing a D-
amino acid, and its pharmacological activity in a number of assays was found to be quite impressive and superior to
morphine. Moreover, it has been established as more selective and potent with long-lasting
analgesia compared to
morphine after intracerebroventricular administration in animal models. In 1985, the first clinical trial results of a randomized, placebo-controlled study in
postoperative pain were reported, and
dermorphin administered via the intrathecal route was again impressively superior over the placebo and the reference compound
morphine. This milestone study was apparently minimally read by clinicians, as the study has never been referenced; only 15 pharmacological and review papers after 1985 mentioned the results, with not one being a clinical paper. The interest in
dermorphin decreased after 1985, and the compound was never again introduced in the clinical setting. Considering the enormous pressure to find superior acting
opioids, this is quite puzzling. We suggest new clinical studies to further evaluate the safety and efficacy of
dermorphin, especially administered via the intrathecal route in
postoperative pain or for palliative use in terminal patients.