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- W1856558418 abstract "The electrically evoked overflow of dopamine (DA) from perfused rabbit striatal slices was used to assess the relative functional potencies of thioridazine, a phenothiazine antipsychotic agent, and two of its major metabolites, mesoridazine (thioridazine-2-sulfoxide) and sulforidazine (thioridazine-2-sulfone). Thioridazine (1000 nM) enhanced the electrically evoked overflow of DA by 18.3 +/- 4.6% (n = 4) at 0.3 Hz. Mesoridazine and sulforidazine likewise produced only small increases (5-20%) in evoked overflow of DA from slices stimulated at 0.3 Hz. At this frequency of stimulation, apomorphine (30 nM) inhibited the overflow of DA by 71.4 +/- 8.43% (n = 40). All three drugs antagonized, in a concentration-dependent fashion, the inhibitory effect of apomorphine (30 nM) on electrically evoked DA release at 0.3 Hz. The IC50 for thioridazine for antagonizing the effect of apomorphine was 130 nM, whereas that for mesoridazine was 14.4 nM and for sulforidazine was 6.1 nM. These results indicate that thioridazine and its two clinically active metabolites can block striatal DA autoreceptors involved in modulating DA release. The observation that mesoridazine and sulforidazine were significantly more potent than the parent drug is consistent with the hypothesis that a major part of the pharmacologic responses to thioridazine may be a consequence of its metabolism to active compounds." @default.
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- W1856558418 date "1984-03-01" @default.
- W1856558418 modified "2023-09-23" @default.
- W1856558418 title "Greater potency of mesoridazine and sulforidazine compared with the parent compound, thioridazine, on striatal dopamine autoreceptors." @default.
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