The improved multigram-scale syntheses of the important 8-styrylxanthine A_2A adenosine receptor antagonist MSX-2 (8), its water-soluble prodrug MXS-3 (9), and KW-6002 (16) are described. N-Alkylation reactions at different positions of uracil derivatives were optimized. Two different methods for xanthine formation from 6-amino-5-cinnamoylaminouracil precursors were investigated, (a) the elimination of water by alkaline catalysis and (b) hexamethyldisilazane as a condensing agent; the latter was found to be superior. The photosensitivity of 8-styrylxanthines was studied. The (E)-configurated stryrylxanthine MSX-2 (8) isomerized in diluted solution, and the resulting (Z)-isomer (10a) was isolated and characterized. Furthermore, we describe for the first time that solid 8-styrylxanthines can dimerize upon exposition to daylight or irradiation with UV light. The resulting cyclobutane derivatives with head-to-tail (syn) configuration exhibited a considerably lower A_2A adenosine receptor affinity than their parent compounds. The dimerization product of MSX-2 was a moderately potent nonselective A₁ and A_2A antagonist (K_i(A₁) = 273 nM, K_i (A_2A) = 175 nM) while the dimer of the related compound KW-6002 was inactive at A₁ and only weakly active at A_2A adenosine receptors (K_i = 1.57 μM). The light sensitivity of 8-styrylxanthine derivatives, not only in solution, but also in the solid state, has to be considered when using those compounds as pharmacological tools or drugs.