Physical dependence liability of dynorphin A analogs in rodents.

Abstract

To assess the physical dependence liability of dynorphin A analogs, mice were given repeated injections of various dynorphin A analogs twice daily for 5 days, and rats were given repeated administration of [N-methyl-Tyr1,N-methyl-Arg7,D-Leu8]dynorphin-A-(1-8) ethylamide (E-2078) twice daily for up to 7 weeks. Mice that had received repeated [D-Cys2,Cys5,N-methyl-Arg7,D-Leu8]dynorphin-A-(1-9) amide displayed jumping behavior after subcutaneous injection of naloxone, an opioid receptor antagonist. In contrast, the animals that had received repeated E-2078 or [N-methyl-Tyr1,Phe4(p-NO2),N-methyl-Arg7,D-Leu8]dynorphin-A-(1-8) ethylamide displayed very few jumps after naloxone administration. Rats that had received repeated E-2078 administration did not display withdrawal signs, such as weight loss, after either abrupt withdrawal or naloxone administration. These results indicate that E-2078 and [N-methyl-Tyr1,Phe4(p-NO2),N-methyl-Arg7,D-Leu8]dynorphin-A-(1-8) ethylamide may have little dependence liability and that [D-Cys2,Cys5,N-methyl-Arg7,D-Leu8]dynorphin-A-(1-9) amide can cause physical dependence.

• Authors: T Nakazawa, T Kaneko, H Yoshino, S Tachibana, M Goto, T Taki, K Yamatsu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 201 Issue 2-3 Pg. 185-9 (Aug 29 1991) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1686757 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Analgesics
• Peptide Fragments
• E 2078
• dynorphin A amide (1-9), Cys(2)-Cys(5)-MeArg(7)-Leu(8)-
• dynorphin A ethylamide (1-8), N-methyl-Tyr(1)-4-nitro-Phe(4)-N-methyl-Arg(7)-Leu(8)-
• Naloxone
• Dynorphins

Topics

• Analgesics (administration & dosage, pharmacology)
• Animals
• Dynorphins (administration & dosage, analogs & derivatives, pharmacology)
• Injections, Subcutaneous
• Male
• Mice
• Mice, Inbred Strains
• Naloxone (pharmacology)
• Peptide Fragments (administration & dosage, pharmacology)
• Rats
• Rats, Inbred Strains
• Substance Withdrawal Syndrome (psychology)
• Substance-Related Disorders (psychology)