Suppression of rat adjuvant arthritis by some acyclic nucleotide analogs

The antiarthritic potential of two different acyclic nucleotide analogs, i.e. 9-(2-phosphonomethoxyethyl)adenine (PMEA), its bis(pivaloyloxymethyl)ester (Bis-POM-PMEA), and 1-(S)-(3-hydroxy-2-phosphonomethoxyethyl) cytosine (HPMPC) was investigated in the rat model of mycobacterial adjuvant-induced arthritis. With dependence on the dose, timing and route of administration, as well as on the genetic constitution of the arthritis-prone animals, PMEA was able to delay the onset, and substantially reduce or nearly completely inhibit the development of arthritic paw swelling. HPMPC was less active in this model. As compared with PMEA, its prodrug, Bis-POM-PMEA, expressed much more pronounced beneficial effects after both oral and i.p. administration.