The selective adenosine A2 receptor agonist, CGS 21680, is a potent depressant of cerebral cortical neuronal activity.

The A2 selective adenosine receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) depressed the spontaneous, acetylcholine- and glutamate-evoked firing of rat cerebral sensorimotor cortical neurons. Iontophoretically applied CGS 21680 was equipotent with adenosine as a depressant and its actions were antagonized by 8-p-sulphophenyltheophylline applied from another barrel of the multibarrelled micropipette. The observation of a potent depressant action of a selective A2 receptor agonist suggests that A2 receptors are involved in the modulation of cerebral cortical neuronal firing by adenosine.