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 raclopri de (1.2 mg/kg, i.p.) in comparison to metoclopramide (5 mg/kg, itp.) o n the extracellular levels of DA and its metabolites using microdialys is 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 inh ibition of L-DOPA decarboxylase (NSD-1015 model) in the rat striatum w ere also investigated. All the drugs studied increased significantly D A 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 increasi ng both DA and its metabolite extracellular levels. It is suggested th at typical and atypical neuroleptics may differentially affect dopamin e release and synthesis in rat striatum.