Basic and clinical aspects of adenosinergic neuromodulation.

Adenosine and the methylxanthines have marked and opposite effects on behavior both of which are now thought to be mediated by cell surface adenosine receptors present in brain. These receptor sites have now been characterized using simple radioreceptor ligand binding techniques. Pharmacologic, autoradiographic and behavioral studies involving adenosine and the methylxanthines strongly suggest a neuromodulatory role for adenosine and indicate that adenosinergic neurons constitute an important central nervous system depressant system. A key component of the adenosinergic system is the adenosine uptake site which represents the inactivation mechanism for receptor mediated adenosine action. The adenosine uptake site can be identified as distinct from the adenosine receptor using a specific ligand. The two key components of the adenosine system, i.e., the receptor and uptake site, can therefore be studied using simple binding techniques. This should facilitate the development of new drugs specific for each system. Adenosine agonists can be expected to have sedative, anticonvulsant and anxiolytic actions whereas adenosine antagonists such as caffeine have stimulant and anxiogenic properties. Adenosine uptake blockers should have pharmacologic actions similar to adenosine agonists. The adenosinergic system, therefore, offers unique opportunities for developing new and potentially useful clinical agents.