Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain.

Abstract

AIM:

To characterize the antinociceptive action of the novel melatonin receptor (MT) agonists, Neu-P11 and Neu-P12 in animal models of visceral pain.

METHODS:

Visceral pain was induced by intracolonic (ic) application of mustard oil or capsaicin solution or by intraperitoneal (ip) administration of acetic acid. Neu-P11, Neu-P12, or melatonin were given ip or orally and their effects on pain-induced behavioral responses were evaluated. To identify the receptors involved, the non-selective MT1/MT2 receptor antagonist luzindole, the MT2 receptor antagonist 4-P-PDOT, or the μ-opioid receptor antagonist naloxone were injected ip or intracerebroventricularly (icv) prior to the induction of pain.

RESULTS:

Orally and ip administered melatonin, Neu-P11, and Neu-P12 reduced pain responses in a dose-dependent manner. Neu-P12 was more effective and displayed longer duration of action compared to melatonin. The antinociceptive effects of Neu-P11 or Neu-P12 were antagonized by ip or icv. administered naloxone. Intracerebroventricularly, but not ip administration of luzindole or 4-P-PDOT blocked the antinociceptive actions of Neu-P11 or Neu-P12.

CONCLUSION:

Neu-P12 produced the most potent and long-lasting antinociceptive effect. Further development of Neu-P12 for future treatment of abdominal pain seems promising.

• Authors: Chunqiu Chen, Jakub Fichna, Moshe Laudon, Martin Storr
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 5 Pg. 1298-304 (Feb 07 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 24574803 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Indoles
• Narcotic Antagonists
• Pyrans
• Receptors, Melatonin
• Melatonin
• N-(2-(5-methoxy-indol-3-yl)-ethyl)-4-oxo-4H-pyran-2-carboxamide

Topics

• Abdominal Pain (chemically induced, diagnosis, metabolism, physiopathology, prevention & control)
• Administration, Oral
• Analgesics (administration & dosage, pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Indoles (administration & dosage, pharmacology)
• Injections, Intraperitoneal
• Injections, Intraventricular
• Male
• Melatonin (pharmacology)
• Mice
• Narcotic Antagonists (pharmacology)
• Pain Measurement
• Pain Threshold (drug effects)
• Pyrans (administration & dosage, pharmacology)
• Receptors, Melatonin (agonists, metabolism)
• Time Factors