The effect of various centrally active drugs on adenosine uptake by the central nervous system.

1. Adenosine and its analogs depress the firing of neurons in various brain regions. The primary mode of action of adenosine in exerting this effect appears to be the depression of transmitter release from presynaptic nerve terminals. This is a result of reduced calcium mobilization. 2. Adenosine uptake inhibitors and deaminase inhibitors depress the firing of central neurons. Adenosine antagonists, caffeine and theophylline, excite central neurons. Adenosine is therefore likely to be released in sufficient quantities to exert an ongoing modulation of synaptic transmission in the intact brain. 3. A number of groups of centrally active drugs inhibit adenosine uptake by brain synaptosomal preparations. These include the benzodiazepines, phenothiazines, various other sedatives and hypnotics, tricyclic antidepressants, non-steroidal anti-inflammatory analgesics, some steroids, diphenylhydantoin, puromycin and toyocamycin. 4. It is proposed that many agents with anxiolytic, sedative, analgesic or anti-convulsant actions may achieve their effects by inhibiting adenosine uptake and thus potentiating extracellular adenosine levels. 5. Morphine also elevates extracellular adenosine levels but achieves this by enhancing adenosine release.