Chlorpromazine and trifluoperazine potentiate the action of adenosine on rat cerebral cortical neurons.

The effect of chlorpromazine and trifluoperazine on adenosine-evoked depressions of the spontaneous firing of rat cerebral cortical neurons has been studied. When applied by iontophoresis from multiple barrelled micropipettes, in amounts that did not affect neuronal firing rates, both substances enhanced the depressant actions of adenosine. Trifluoperazine did not enhance the depressant actions of the uptake resistant analog, adenosine 5'-N-ethylcarboxamide. Intravenously administered chlorpromazine and trifluoperazine (1 mg/kg) enhanced the depressant actions of iontophoretically applied adenosine. Caffeine antagonized the depressant effect on the firing of cortical neurons observed with larger applications of trifluoperazine. These findings support the conclusion, drawn from previous studies on the effects of phenothiazines on the uptake of adenosine by brain synaptosomes, that inhibition of adenosine uptake and potentiation of the actions of endogenously released adenosine may be a significant factor in the generation of the central actions of the phenothiazines.