Effect of long-term dosing with tiapride on brain dopamine receptors and metabolism in rats. Comparative study with sulpiride and haloperidol.

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The effects of long-term dosing with tiapride for 21 days on barin dopamine receptors and dopamine turnover were compared with those of sulpiride and haloperidol. Haloperidol caused an increase in both antagonist (<SUP>3</SUP>H-spiperone) labeled receptors and agonist (<SUP>3</SUP>H-N, n-propylnorapomorphine) labeled ones, whereas tiapride acted on the agonist binding sites and sulpiride acted on the antagonist binding sites. The increases induced by sulpiride were only observed in the striatum, while those induced by tiapride and haloperidol were observed in both the striatum and limbic area. Dopamine and dopamine metabolites in the brain tissues were measured at 2 hr and 3 days after long-term dosing with the drugs as an indicator of dopamine turnover. They were higher at 2 hr and lower at 3 days than those of the saline treated controls, however, the increase at 2 hr was much less than that after single acute dosing with drugs. This suggested that all drugs induced tolerance with regard to dopamine turnover. In these studies, tiapride and sulpiride were less active than haloperidol in the effects on brain dopamine receptors and dopamine turnover. This generally weaker activity of sulpiride and tiapride suggest that the benzamide drugs have fewer side effects such as a tardive dyskinesia, than does haloperidol, even after long-term dosing. Furthermore, a slight difference between the effects of tiapride and sulpiride on the dopamine receptor subtypes in the brain subdivision was suggested.
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Effect of long-term dosing with tiapride on brain dopamine receptors and metabolism in rats. Comparative study with sulpiride and haloperidol.

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