PMID- 7712029
OWN - NLM
STAT- MEDLINE
DCOM- 19950517
LR  - 20190512
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 114
IP  - 1
DP  - 1995 Jan
TI  - Production of antinociception by peripheral administration of [Lys7]dermorphin, a 
      naturally occurring peptide with high affinity for mu-opioid receptors.
PG  - 57-66
AB  - 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.
FAU - Negri, L
AU  - Negri L
AD  - Institute of Medical Pharmacology, University La Sapienza, Roma, Italy.
FAU - Lattanzi, R
AU  - Lattanzi R
FAU - Melchiorri, P
AU  - Melchiorri P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Oligopeptides)
RN  - 0 (Opioid Peptides)
RN  - 0 (Receptors, Opioid, mu)
RN  - 2SEC01B703 (dermorphin)
RN  - 36B82AMQ7N (Naloxone)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Analgesics, Opioid/pharmacology
MH  - Animals
MH  - Body Weight/drug effects
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Tolerance
MH  - Male
MH  - Mice
MH  - Morphine/pharmacology
MH  - Naloxone/pharmacology
MH  - Nociceptors/*drug effects/physiology
MH  - Oligopeptides/*pharmacology
MH  - Opioid Peptides
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Opioid, mu/*drug effects/physiology
MH  - Substance-Related Disorders/metabolism
PMC - PMC1510172
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
PMCR- 1996/01/01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
PHST- 1996/01/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1995.tb14905.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1995 Jan;114(1):57-66. doi: 10.1111/j.1476-5381.1995.tb14905.x.