REMOXIPRIDE AND RACLOPRIDE DIFFER FROM METOCLOPRAMIDE BY THEIR EFFECTS ON STRIATAL DOPAMINE RELEASE AND BIOSYNTHESIS IN RATS

Effects of new neuroleptics remoxipride (2.4 mg/kg, i.p.) and raclopride (1.2 mg/kg, i.p.) in comparison to metoclopramide (5 mg/kg, itp.) on the extracellular levels of DA and its metabolites using microdialysis technique in freely moving rats were-studied. The effects of these drugs as well as that of cis- and trans-carbidine (25 and 1 mg/kg, i.p., respectively), sulpiride (50 mg/kg, i.p.) and haloperidol (1 mg/kg, i.p.) on the DA biosynthesis rate by accumulation of L-DOPA after inhibition of L-DOPA decarboxylase (NSD-1015 model) in the rat striatum were also investigated. All the drugs studied increased significantly DA biosynthesis rate. The order of potency of drugs was: metoclopramide > haloperidol > raclopride > remoxipride > sulpiride > cis-carbidine > trans-carbidine. In microdialysis study metoclopramide was shown to produce much greater increase in HVA and DOPAC and only modest rise in DA levels. Meanwhile remoxipride and raclopride were found to differ from the former drug being approximately equally effective in increasing both DA and its metabolite extracellular levels. It is suggested that typical and atypical neuroleptics may differentially affect dopamine release and synthesis in rat striatum.