Protective effects of D-penicillamine and a thiazole derivative, SM-8849, on pristane-induced arthritis in mice.

Abstract

To evaluate the antiarthritic properties of a novel thiazole derivative, the drugs SM-8849, D-penicillamine and indomethacin were administered to pristane-injected DBA/1 mice. The mice were treated daily with the agents for 32 weeks, starting from the day of the pristane injection. Treatment with SM-8849 (50 mg/kg) resulted in an amelioration of arthritic disease, as assessed by clinical, radiographic, and histologic examinations. Similar results were obtained in mice treated with 50 mg/kg D-penicillamine, although this disease modifying antirheumatic drug was slightly less effective than the same dose of SM-8849. In contrast, indomethacin at the maximum tolerated dose of 2 mg/kg did not alter the course of the disease. SM-8849 and D-penicillamine were also shown to reduce serum levels of rheumatoid factors and the acute-phase reactant, serum amyloid P component. Indomethacin failed to affect either parameter. Flow cytometric analysis revealed an elevation in the T-cell population that expressed CD44, a marker of murine memory T-cells, in spleens from pristane-injected mice. SM-8849, but not D-penicillamine, prevented the increase in this cell population. These results led us to conclude that pristine-induced arthritis was a useful model for the evaluation of antirheumatic agents, in that using this model, we were able to distinguish disease modifying antirheumatic drugs from nonsteroidal anti-inflammatory drugs. Our findings also indicate that SM-8849 shows antiarthritic activity, with a unique mechanism of action, differing from that of D-penicillamine.

• Authors: F Nishikaku, S Aono, Y Koga
• Journal: International journal of immunopharmacology (Int J Immunopharmacol) Vol. 16 Issue 2 Pg. 91-100 (Feb 1994) ISSN: 0192-0561 [Print] England
• PMID: 7514159 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Biphenyl Compounds
• Carrier Proteins
• Hyaluronan Receptors
• Receptors, Cell Surface
• Receptors, Lymphocyte Homing
• Terpenes
• Thiazoles
• 4-(1-(2-fluoro-4-biphenyl)ethyl)-2-methylaminothiazole
• pristane
• Penicillamine

Topics

• Adjuvants, Immunologic (therapeutic use)
• Animals
• Arthritis (chemically induced, drug therapy, immunology)
• Biphenyl Compounds (therapeutic use)
• Carrier Proteins (analysis)
• Hyaluronan Receptors
• Male
• Mice
• Mice, Inbred DBA
• Penicillamine (therapeutic use)
• Receptors, Cell Surface (analysis)
• Receptors, Lymphocyte Homing (analysis)
• T-Lymphocytes (immunology)
• Terpenes
• Thiazoles (therapeutic use)