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, Victor J Hruby, G. Bowden, C. A. Cullinan, T. F. Burks

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 - 1994
Externally publishedYes

Fingerprint

mu Opioid Receptor
Analgesics
delta Opioid Receptor
Narcotic Antagonists
Cholecystokinin B Receptor
aspartyltyrosine
aspartyl-phenylalanine
Cholecystokinin Receptors
Sincalide
kappa Opioid Receptor
Enkephalins
Cholecystokinin
SNF 9007
Tail
Water
Brain

ASJC Scopus subject areas

  • Pharmacology

Cite this

Williams, C. L., Rosenfeld, G. C., Dafny, N., Fang, S. N., Hruby, V. J., Bowden, G., ... 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.

SNF9007 : A novel analgesic that acts simultaneously at delta1, delta2 and mu opioid receptors. / Williams, C. L.; Rosenfeld, G. C.; Dafny, N.; Fang, S. N.; Hruby, Victor J; Bowden, G.; Cullinan, C. A.; Burks, T. F.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 269, No. 2, 1994, p. 750-755.

Research output: Contribution to journalArticle

Williams, CL, Rosenfeld, GC, Dafny, N, Fang, SN, Hruby, VJ, Bowden, G, Cullinan, CA & Burks, TF 1994, 'SNF9007: A novel analgesic that acts simultaneously at delta1, delta2 and mu opioid receptors', Journal of Pharmacology and Experimental Therapeutics, vol. 269, no. 2, pp. 750-755.
Williams, C. L. ; Rosenfeld, G. C. ; Dafny, N. ; Fang, S. N. ; Hruby, Victor J ; Bowden, G. ; Cullinan, C. A. ; Burks, T. F. / SNF9007 : A novel analgesic that acts simultaneously at delta1, delta2 and mu opioid receptors. In: Journal of Pharmacology and Experimental Therapeutics. 1994 ; Vol. 269, No. 2. pp. 750-755.
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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.",
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AU - Hruby, Victor J

AU - Bowden, G.

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