Metoclopramide and sulpiride as selective blocking agents of pre- and postsynaptic dopamine receptors.

1. The effects of sulpiride and metoclopramide on pre- and postsynaptic dopamine receptors were investigated in the rat brain as antagonism of the apomorphine-induced inhibition of the dopamine synthesis in the absence of nerve impulses and as blockade of the apomorphine-induced rotation following unilateral inactivation of the corpus striatum, respectively. Sulpiride was more potent in blocking post- than presynaptic dopamine receptors whereas the reverse was found for metoclopramide. 2. The synthesis and the utilization of dopamine was stimulated by sulpiride and metoclopramide and was inhibited by atropine, prazosin and aminooxyacetic acid. The inhibitory effects of the latter three drugs were counteracted by metoclopramide, but not by sulpiride. This difference can be explained by the preferential action of metoclopramide on presynaptic dopamine receptors. 3. Following unilateral inactivation of the corpus striatum, metoclopramide at a low dose, but not sulpiride turned the rats ipsilaterally, indicating that the release of dopamine was facilitated and that the presynaptic dopamine receptors are of physiological significance.