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. 1988 Sep;95(1):15–22. doi: 10.1111/j.1476-5381.1988.tb16543.x

Antinociception and physical dependence produced by [D-Arg2] dermorphin tetrapeptide analogues and morphine in rats.

K Chaki 1, S Kawamura 1, K Kisara 1, S Sakurada 1, T Sakurada 1, Y Sasaki 1, T Sato 1, K Susuki 1
PMCID: PMC1854126  PMID: 2905901

Abstract

1. The antinociceptive effects of [D-Arg2] dermorphin tetrapeptide analogues, H-Tyr-D-Arg-Phe-Gly-NH2 and H-Tyr-D-Arg-Phe-beta-Ala-OH when administered subcutaneously (s.c.) in rats were measured by the tail-flick test. In addition, the appearance of typical withdrawal signs upon cessation of administration or on subsequent treatment with naloxone were measured after chronic administration of either peptide or morphine. 2. The dose of peptides and of morphine in the physical dependence test was determined from the AD50 to inhibit the tail-flick test in rats. Doses from 4 to 64 times the AD50 doses were employed in the s.c. administration schedules. 3. The intensity of the antinociception induced by either peptide was greater than that produced by morphine. Moreover, the antinociception induced by the peptides was of much longer duration than that produced by morphine. 4. Abrupt withdrawal after chronic administration of either peptide produced only slight loss of body weight. In contrast, morphine withdrawal produced sharp loss of body weight. 5. Naloxone precipitated withdrawal signs after chronic administration of either peptide were less intense than those after chronic morphine. 6. These results suggest that the antinociception produced by these peptides is more intense and of longer duration than that produced by morphine. It is also interesting to note that the physical dependence produced by these peptides is less marked than that produced by morphine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akera T., Brody T. M. The addiction cycle to narcotics in the rat and its relation to catecholamines. Biochem Pharmacol. 1968 May;17(5):675–688. doi: 10.1016/0006-2952(68)90004-x. [DOI] [PubMed] [Google Scholar]
  2. Broccardo M., Erspamer V., Falconieri Erspamer G., Improta G., Linari G., Melchiorri P., Montecucchi P. C. Pharmacological data on dermorphins, a new class of potent opioid peptides from amphibian skin. Br J Pharmacol. 1981 Jul;73(3):625–631. doi: 10.1111/j.1476-5381.1981.tb16797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Erspamer V., Melchiorri P., Broccardo M., Erspamer G. F., Falaschi P., Improota G., Negri L., Renda T. The brain-gut-skin triangle: new peptides. Peptides. 1981;2 (Suppl 2):7–16. doi: 10.1016/0196-9781(81)90003-6. [DOI] [PubMed] [Google Scholar]
  4. Feuerstein G., Faden A. I. Central autonomic effects of dermorphin in conscious rats. J Pharmacol Exp Ther. 1983 Jul;226(1):151–156. [PubMed] [Google Scholar]
  5. Frederickson R. C., Smits S. E. Time course of dependence and tolerance development in rats treated with "slow release" morphine suspensions. Res Commun Chem Pathol Pharmacol. 1973 May;5(3):867–870. [PubMed] [Google Scholar]
  6. Goode P. G. An implanted reservoir of morphine solution for rapid induction of physical dependence in rats. Br J Pharmacol. 1971 Mar;41(3):558–566. doi: 10.1111/j.1476-5381.1971.tb08054.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Güllner H. G., Kelly G. D. Dermorphin: effects on anterior pituitary function in the rat. Arch Int Pharmacodyn Ther. 1983 Apr;262(2):208–214. [PubMed] [Google Scholar]
  8. Judson B. A., Himmelberger D. U., Goldstein A. The naloxone test for opiate dependence. Clin Pharmacol Ther. 1980 Apr;27(4):492–501. doi: 10.1038/clpt.1980.69. [DOI] [PubMed] [Google Scholar]
  9. Kawamura S., Sakurada S., Sakurada T., Kisara K., Akutsu Y., Sasaki Y., Suzuki K. Antinociceptive effect of centrally administered cyclo(N-methyl-L-Tyr-L-Arg) in the rat. Eur J Pharmacol. 1983 Sep 16;93(1-2):1–8. doi: 10.1016/0014-2999(83)90024-9. [DOI] [PubMed] [Google Scholar]
  10. Kisara K., Sakurada S., Sakurada T., Sasaki Y., Sato T., Suzuki K., Watanabe H. Dermorphin analogues containing D-kyotorphin: structure-antinociceptive relationships in mice. Br J Pharmacol. 1986 Jan;87(1):183–189. doi: 10.1111/j.1476-5381.1986.tb10170.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Montecucchi P. C., de Castiglione R., Erspamer V. Identification of dermorphin and Hyp6-dermorphin in skin extracts of the Brazilian frog Phyllomedusa rhodei. Int J Pept Protein Res. 1981 Mar;17(3):316–321. doi: 10.1111/j.1399-3011.1981.tb01997.x. [DOI] [PubMed] [Google Scholar]
  12. Mordes J. P., Eastwood G. L., Loo S., Rossini A. A. Pancreatic polypeptide causes diarrhea and weight loss in obese mice but not in lean littermates. Peptides. 1982 Sep-Oct;3(5):873–875. doi: 10.1016/0196-9781(82)90030-4. [DOI] [PubMed] [Google Scholar]
  13. Nakata N., Sakurada S., Sakurada T., Kisara K., Sasaki Y., Suzuki K. Physical dependence of a dermorphin tetrapeptide analog, [D-Arg2, Sar4]-dermorphin (1-4) in the rat. Pharmacol Biochem Behav. 1986 Jan;24(1):27–31. doi: 10.1016/0091-3057(86)90039-0. [DOI] [PubMed] [Google Scholar]
  14. Salvadori S., Sarto G., Tomatis R. Synthesis and pharmacological activity of dermorphin and its N-terminal sequences. Int J Pept Protein Res. 1982 May;19(5):536–542. doi: 10.1111/j.1399-3011.1982.tb02639.x. [DOI] [PubMed] [Google Scholar]
  15. Sasaki Y., Matsui M., Fujita H., Hosono M., Taguchi M., Suzuki K., Sakurada S., Sato T., Sakurada T., Kisara K. The analgesic activity of D-Arg2-dermorphin and its N-terminal tetrapeptide analogs after subcutaneous administration in mice. Neuropeptides. 1985 Feb;5(4-6):391–394. doi: 10.1016/0143-4179(85)90036-8. [DOI] [PubMed] [Google Scholar]
  16. Sasaki Y., Matsui M., Taguchi M., Suzuki K., Sakurada S., Sato T., Sakurada T., Kisara K. D-Arg2-dermorphin tetrapeptide analogs: a potent and long-lasting analgesic activity after subcutaneous administration. Biochem Biophys Res Commun. 1984 Apr 16;120(1):214–218. doi: 10.1016/0006-291x(84)91435-9. [DOI] [PubMed] [Google Scholar]
  17. Sato T., Sakurada S., Sakurada T., Furuta S., Chaki K., Kisara K., Sasaki Y., Suzuki K. Opioid activities of D-Arg2-substituted tetrapeptides. J Pharmacol Exp Ther. 1987 Aug;242(2):654–659. [PubMed] [Google Scholar]
  18. de Castiglione R., Faoro F., Perseo G., Piani S., Santangelo F., Melchiorri P., Falconieri Erspamer G., Erspamer V., Guglietta A. Synthetic peptides related to the dermorphins. I. Synthesis and biological activities of the shorter homologues and of analogues of the heptapeptides. Peptides. 1981 Fall;2(3):265–269. doi: 10.1016/s0196-9781(81)80117-9. [DOI] [PubMed] [Google Scholar]

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