Antagonism by clonidine of neuronal depressant responses to adenosine, adenosine-5'-monophosphate and adenosine triphosphate.

1. Adenosine and its nucleotides adenosine-5'-monophosphate (AMP) and adenosine triphosphate (ATP) have been applied by microiontophoresis to neurones in the cerebral cortex of rats anesthetized with urethane. The firing rate of most neurones was depressed, though two cells were encountered which showed biphasic responses to ATP consisting of an initial excitation succeeded by depression. 2. The application of clonidine with iontophoretic currents of less than 25 nA resulted in blockade of the depressant responses to the purines, without affecting responses to noradrenaline, 5-hydroxytryptamine or gamma-aminobutyric acid (GABA). At much higher doses of clonidine, direct depression of cell firing occurred and occasional interaction with noradrenaline was noted. 3. In the case of the biphasic responses to ATP, clonidine seemed to block only the depressant phase. Reduction of the excitatory component paralleled changes of background firing. 4. It is concluded that, in common with some other 2-substituted imidazoline derivatives, clonidine possesses the ability to block responses to purine compounds.