L -DOPA–Chlorpromazine Antagonism on Running Activity in Mice

An attempt was made to study the nature of the antagonistic effect of chlorpromazine on running activity induced by L-3, 4-dihydroxyphenylalanine (L-DOPA) in mice. Dose–effect relations for L-DOPA, given alone and in combination with chlorpromazine, were determined in male albino mice pretreated with an inhibitor of the extracerebral aromatic L-amino acid decarboxylase. Chlorpromazine produced a marked depression in the maximal running response to L-DOPA and a flattening in the slope of the L-DOPA dose–response curve. The results are compatible with a noncompetitive blockade of central dopamine receptors by chlorpromazine as the main mechanism of the drug's anti-L-DOPA activity.