Antinociceptive properties of FR140423 mediated through spinal delta-, but not mu- and kappa-, opioid receptors.

Abstract

We investigated the antinociceptive effect of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl] pyrazole, in the tail-pinch test in mice, and evaluated the mechanism of action using various opioid receptor antagonists. P.o. and i.t. injection of FR140423 exerted dose-dependent antinociceptive activities with ED50 values of 21 mg/kg and 3.1 microg/mouse, respectively. However, i.c.v. injection of FR140423 did not show an antinociceptive effect. The antinociceptive effects of FR140423 were completely abolished by naloxone and naltrindole but not by naloxonazine, beta-funaltrexamine and nor-binaltorphimine. FR140423 did not affect any opioid receptor binding in mouse spinal membranes at concentrations up to 100 microM in vitro. Naloxone-induced jumping and diarrhea tests for morphine-like physical dependence of FR140423 gave negative results. These results suggest that FR140423 can induce antinociception by acting on the spinal but not the supraspinal site, and that spinal delta-opioid systems indirectly play a role in the antinociception produced by FR140423 in mice.

• Authors: T Ochi, T Fujii, Y Motoyama, T Goto
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 380 Issue 2-3 Pg. 73-9 (Sep 10 1999) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10513565 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Anti-Inflammatory Agents, Non-Steroidal
• Narcotic Antagonists
• Pyrazoles
• Receptors, Opioid
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• Receptors, Opioid, mu
• Sulfoxides
• 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-(4-(methylsulfinyl)phenyl)pyrazole
• Naloxone
• norbinaltorphimine
• Naltrexone
• beta-funaltrexamine
• naloxonazine
• naltrindole

Topics

• Administration, Oral
• Analgesics (pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Behavior, Animal (drug effects)
• Binding, Competitive (drug effects)
• Diarrhea (chemically induced)
• Injections, Intraventricular
• Injections, Spinal
• Male
• Membranes (drug effects, metabolism)
• Naloxone (analogs & derivatives, pharmacology)
• Naltrexone (analogs & derivatives, pharmacology)
• Narcotic Antagonists (pharmacology)
• Pain (physiopathology, prevention & control)
• Pain Measurement
• Pyrazoles (pharmacology)
• Rats
• Receptors, Opioid (physiology)
• Receptors, Opioid, delta (physiology)
• Receptors, Opioid, kappa (physiology)
• Receptors, Opioid, mu (physiology)
• Spinal Cord (drug effects, metabolism)
• Sulfoxides