1. The
opioid activity of the amphibian
peptide, [Lys7]
dermorphin, was studied in rats and mice. When administered intracerebroventricularly (i.c.v.), intravenously (i.v.) or subcutaneously (s.c.) it produced a long lasting
analgesia. Its antinociceptive potency exceeded that of
morphine 290 times by i.c.v. injection, and 25-30 times by peripheral administration. 2. The dose-response curves of [Lys7]
dermorphin antinociception were shifted to the right by the pretreatment with
naloxone (0.1 mg kg-1, s.c.) or with the mu 1-selective antagonist,
naloxonazine (10 mg kg-1, i.v. 24 h before
peptide injection). 3. The
peptide also displayed potent antinociceptive effects in a chronic inflammatory
pain model (rat
Freund's adjuvant arthritis). In this
pain model, systemic administration of the
peptide raised the nociceptive threshold more in inflamed than in healthy paw. 4. High central and peripheral doses of [Lys7]
dermorphin in rats produced
catalepsy. The cataleptic response was antagonized by
naloxone but left unchanged by
naloxonazine pretreatment. 5. In rats and mice, central or peripheral administration of [Lys7]
dermorphin induced a significantly slower development of tolerance to the antinociceptive effect than did
morphine. 6. Upon
naloxone precipitation of the withdrawal syndrome, [Lys7]
dermorphin-dependent mice made fewer jumps and lost less weight than the
morphine-dependent animals. Withdrawal
hyperalgesia did not develop in [Lys7]
dermorphin-dependent mice. 7. In conclusion, [Lys7]
dermorphin seems to be a unique
opioid peptide having a high penetration into the blood-brain barrier despite its low
lipid solubility. This
peptide causes fewer side-effects than other
opioids and appears less likely than
morphine to cause physical dependence in rats and mice.