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Lack of potency of metoclopramides metabolites in various dopaminergic models

, : Lack of potency of metoclopramides metabolites in various dopaminergic models. Pharmacology Biochemistry & Behavior 18(2): 263-266

The dopaminergic properties of metoclopramide and 4 of its metabolites were determined in a series of in vivo and in vitro tests. In vivo measures included changes in dopamine turnover, serum prolactin levels and antagonism of apomorphine-induced stereotyped behavior in rats. In each of these tests the 4 metabolites were either completely inactive or significantly less potent than the parent compound. The potency of metoclopramide and its metabolites in in vitro dopamine/neuroleptic receptor models was compared to the potency of standard reference compounds. In vitro results indicate that none of the 4 metabolites tested had antagonist activity in any of the receptor models in which they were evaluated. These findings with be discussed in light of the current understanding of receptor models as they relate to antipsychotic efficacy.


PMID: 6682229

DOI: 10.1016/0091-3057(83)90372-6

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