Intrathecal dermorphine in postoperative analgesia

This randomized clinical trial, conducted in Italy by Nicola Basso and colleagues, was the first controlled study in humans to evaluate the analgesic efficacy of dermorphin — the potent opioid heptapeptide isolated by Erspamer from the skin of Phyllomedusa frogs. The context was to explore whether the D-amino acid at position 2 and high μ-opioid selectivity would translate into clinical advantages over established opioids.

The study included 150 patients undergoing elective surgery, randomized into three groups: (1) intrathecal dermorphin 20 µg, (2) intrathecal morphine 500 µg (25-fold higher dose), or (3) intramuscular pentazocine 30 mg (standard regimen of the era). Endpoints evaluated were analgesia intensity and duration, time to rescue analgesia, and occurrence of typical opioid adverse effects (urinary retention, vomiting, headache).

Results demonstrated remarkable clinical superiority of dermorphin: mean analgesia duration of 43.41 ± 1.64 hours, compared to 34.45 ± 2.35 hours for intrathecal morphine and only 10.79 ± 2.23 hours for IM pentazocine. Analgesia depth was also superior, and intrathecal patients (dermorphin and morphine) had significantly shorter hospital stays. Crucially, the incidence of adverse effects (urinary retention, vomiting, post-puncture headache) was statistically similar across the three groups.

This trial established dermorphin as a clinically useful long-acting peptide opioid, with analgesic potency by molecular mass several times higher than morphine. Despite initial enthusiasm, dermorphin was never commercially developed due to logistical factors (synthesis cost, regulatory restrictions, absence of a sponsoring company). This work remains historical evidence of the clinical potential of D-amino acid opioid peptides in postoperative and palliative pain management.