Purine Metabolism and Clinical Status of Patients with Rheumatoid Arthritis Treated with Dipyridamole

Abstract

The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.

The Inflammatory Role of Platelets: Translational Insights from Experimental Studies of Autoimmune Disorders

“…Even more surprising, treatment with P2Y 12 receptor antagonists like prasugrel leads to an aggravated disease course [70,73]; however, to support the potential human relevance, several case reports of patients developing spontaneous joint inflammation after clopidogrel intake exist [74,75,76,77,78,79]. Additionally, the effect of dipyridamole was tested as a therapy in RA patients, but it did not modify disease severity [80]. …”

Influence of dipyridamole and its combination with NO donor or NO synthase inhibitor on adjuvant arthritis

“…In the clinical studies, there is only one study has evaluated the effect of dipyridamole alone in rheumatoid patients [10].They reported that rheumatoid patients showed no clinical improvement following treatment with dipyridamole for 6 months. However, more recent articles demonstrated synergistic interaction of dipyridamole as potential adjuvant therapy to low dose of glucocorticoid in the treatment of osteoarthritis [8,26,27] and periodontitis [28].…”

“…A few studies that were designed to test the effect of dipyridamole, a non-specific phosphodiesterase inhibitor, on the pathogenesis of autoimmune diseases [8][9][10]. In the present study, we carefully evaluated the prophylactic and therapeutic potential of dipyridamole, for the treatment of adjuvant-induced arthritis in rats.…”

“…On the contrary, dipyridamole did not modify the symptoms of rheumatoid arthritis in other clinical trial described by Forrest et al [10]. However, in animal models of rheumatoid, it is not clear whether or not dipyridamole has anti-inflammatory and immunomodulating effects and the role played by NO in dipyridamole actions remains to be determined.…”

Identifying disease related sub-pathways for analysis of genome-wide association studies

“…In 16 sub-pathways, there are nine sub-pathways whose entire pathways they include in were also found to be statistically significant (p b 0.05) by an entire pathway identification method (hypergeometric test). Many studies suggest that these nine pathways such as purine metabolism (path: 00230), tight junction (path: 04530), and calcium signaling (path: 04020) are relevant to the pathogenesis of RA (Crupi et al, 2010;Davies and Hallett, 1998;Ewert et al, 2010;Forrest et al, 2006). For example, calcium (Ca 2 + ) signaling was found to play an important role in controlling a diverse range of cellular processes, such as gene transcription, muscle contraction, and cell proliferation (Bootman et al, 2001).…”