[7--C]-()-8-(3,4,5-Trimethoxystyryl)-1,3,7-trimethylxanthine

Adenosine is an endogenous nucleoside that modulates a number of physiologic functions in the central nervous system (CNS) and in peripheral organs such as the heart, kidney, and muscle (1, 2). The effect is mediated by two major subtypes of receptors (A and A receptors) and two minor subtypes (A and A). In the CNS, A receptors are present both pre- and postsynaptically in the hippocampus, cerebral cortex, thalamus, striatum, and cerebellum. A receptors are highly concentrated and co-localized with dopamine D and D receptors in the striatum, nucleus accumbens, and olfactory tubercle. A receptors are also present in low amounts in the hippocampus and cortex. A receptors are widely distributed, but the density is higher in the gastrointestinal tract. A receptors are also widely distributed but with higher density in the testis. A and A receptors mediate inhibition of adenylyl cyclase, whereas A and A receptors mediate stimulation. Changes in the adenosine receptor functions are implicated in epilepsy, ischemic cerebral stroke, movement disorders, sleep disorders, and psychiatric disorders (3-5). A receptors have been studied by positron emission tomography (PET) using [7--C]-()-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([C]TMSX), a methylxanthine analog of KF17387 with selective A antagonistic activity (6). TMSX showed better selectivity for A over A receptors than KF17387 and had little affinity in various neuroreceptor-binding assays (7). [C]TMSX is being developed as a PET agent for the non-invasive study of A receptors in the human brain and heart.