2-Phthalimidethanol and 2-phthalimidethyl nitrate inhibit mechanical allodynia, neutrophil recruitment and cytokine and chemokine production in a murine model of articular inflammation.

Abstract

BACKGROUND:

Phthalimide analogs have been shown to exhibit anti-inflammatory, analgesic and immunomodulatory activities in different preclinical assays. This study aimed to investigate the potential role of 2-phthalimidethanol (PTD-OH) and 2-phthalimidethyl nitrate (PTD-NO) in a murine model of antigen-induced articular inflammation.

METHODS:

Articular inflammation was induced by intra-articular injection of methylated bovine serum albumin (mBSA) in the knee joint of immunized male C57BL/6J mice. The animals were pre-treated with PTD-OH or PTD-NO (500mg/kg, per os, - 1h). Nociceptive threshold was measured using an electronic von Frey apparatus. The total number of leukocytes in the synovial cavity was determined. Concentrations of tumor necrosis factor (TNF)-α and CXCL-1 and myeloperoxidase (MPO) activity were determined in periarticular tissue.

RESULTS:

Both PTD-OH and PTD-NO inhibited at similar extent the mechanical allodynia, neutrophil recruitment to the synovial cavity and periarticular tissue and TNF-α and CXCL-1 production induced by intra-articular challenge with mBSA in immunized mice.

CONCLUSIONS:

PTD-OH and PTD-NO exhibit a marked activity in a murine model of antigen-induced articular inflammation in immunized animals. These results reinforce the interest in the investigation of phthalimide analogs devoid of the glutarimide ring as candidates to analgesic and anti-inflammatory drugs.

• Authors: Adriana M Godin, Débora P Araújo, Raquel R Menezes, Ana M S de Brito, Ivo S F Melo, Giovanna M E Coura, Leandro F S Bastos, Flávio A Amaral, Mauro M Teixeira, Ângelo de Fátima, Márcio M Coelho, Renes R Machado
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 69 Issue 4 Pg. 691-695 (Aug 2017) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 28550800 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chemical References

• 2-phthalimidethanol
• 2-phthalimidethyl nitrate
• Analgesics
• Cytokines
• Phthalimides
• Serum Albumin, Bovine

Topics

• Analgesics (pharmacology)
• Animals
• Cytokines (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Hyperalgesia (prevention & control)
• Joint Diseases (chemically induced, drug therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Structure
• Neutrophils (drug effects)
• Phthalimides (chemistry, pharmacology)
• Serum Albumin, Bovine (immunology)