SNF9007: A novel analgesic that acts simultaneously at delta1, delta2 and mu opioid receptors

C. L. Williams, G. C. Rosenfeld, N. Dafny, S. N. Fang, V. J. Hruby, G. Bowden, C. A. Cullinan, T. F. Burks

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Intracerebroventricular administration of the synthetic cholecystokinin analog SNF9007 (Asp-Tyr-D-Phe-Gly-Trp-[NMe]-Nle-Asp-Phe-NH2) produced antinociception in the mouse hot-plate and warm water tail-flick tests. The mechanisms of its analgesic actions were assessed by administering antagonists selective for CCK (cholecystokinin octapeptide, sulfated)-A and CCK-B receptors, as well as specific antagonists for the mu opioid receptor (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, 1 μg i.c.v.), the delta-1 opioid receptor [D-Ala2-Leu5, Cys6)enkephalin, 4.57 nmol i.c.v., 24 hr pretreatment), the delta-2 opioid receptor (naltrindole benzofuran, 25 pmol i.c.v.) and the kappa opioid receptor (nor-binaltorphimine, 10 mg/kg s.c.). The antinociceptive activity of SNF9007 was not a result of the activation of CCK receptors, as treatment with either CCK-A or CCK-B receptor antagonist was ineffective in blocking SNF9007 antinociception. Nor-binaltorphimine and naltrindole benzofuran were completely ineffective in blocking SNF9007 antinociception when administered alone or in combination. However, co- administration of delta-1 or delta-2 opioid receptor antagonists with the mu opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 resulted in a dramatic reduction in analgesic response to SNF9007. Furthermore, the co-administration of mu + delta-1 + delta-2 opioid receptor antagonists resulted in an even greater inhibition of SNF9007 antinociception (>10-fold shift). We conclude that SNF9007 acts simultaneously at brain delta-1, delta- 2 and mu opioid receptors to induce antinociceptive effects in mice.

Original languageEnglish (US)
Pages (from-to)750-755
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume269
Issue number2
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Williams, C. L., Rosenfeld, G. C., Dafny, N., Fang, S. N., Hruby, V. J., Bowden, G., Cullinan, C. A., & Burks, T. F. (1994). SNF9007: A novel analgesic that acts simultaneously at delta1, delta2 and mu opioid receptors. Journal of Pharmacology and Experimental Therapeutics, 269(2), 750-755.