Historically, the major emphasis on the study of purinergic systems has
been predominantly in the areas of physiology and gross pharmacology.
The last decade has seen an exponential in- crease in the number of
publications related to the role of both adenosine and A TP in mammalian
tissue function, a level of interest that has evolved from a more
molecular focus on the identity of adenosine and A TP receptor subtypes
and the search for selective ligands and development of radioligand
binding assays by Fred Bruns and colleagues (especially that for A
receptors) that played z a highly significant role in advancing research
in the area. In the 60 years since adenosine was first shown to be a
potent hypotensive agent, a considerable investment has been made by
several pharmaceutical companies-including Abbott, Byk Gulden, Takeda,
Warner-LambertlParke Davis, Boehringer Mann- heim, Boehringer Ingelheim,
Nelson/Whitby Research and CffiA- Geigy-as well as John Daly's
laboratory at the National Institutes of Health, to design new adenosine
receptor ligands, and both agon- ists and antagonists with the aim of
developing new therapeutic entiities. Numerous research tools have
derived from these efforts including: 2-chloroadenosine, R-PIA (
-phenylisopropyladeno- sine; NECA (5' N-ethylcarboxamidoadenosine);
CV1808; CI936; PD 125,944; -benzyladenosine; PACPX; CPX; CPT; XAC; CGS
15943 and CGS 21680. Yet in the realm of therapeutics it was only in
1989 that adenosine itself was approved for human use in the treatment
of supraventricular arrythmias.
