SUPPRESSION OF RAT ADJUVANT ARTHRITIS BY SOME ACYCLIC NUCLEOTIDE ANALOGS

The antiarthritic potential of two different acyclic nucleotide analog s, i.e. 9-(2-phosphonomethoxyethyl)adenine (PMEA), its bis(pivaloyloxy methyl)ester (Bis-POM-PMEA), and 1-(S)-(3-hydroxy-2-phosphonomethoxyet hyl) cytosine (HPMPC) was investigated in the rat model of mycobacteri al adjuvant-induced arthritis. With dependence on the dose, timing and route of administration, as well as on the genetic constitution of th e arthritis-prone animals, PMEA was able to delay the onset, and subst antially reduce or nearly completely inhibit the development of arthri tic paw swelling. HPMPC was less active in this model. As compared wit h PMEA, its prodrug, Bis-POM-PMEA, expressed much more pronounced bene ficial effects after both oral and i.p. administration.