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  • Title: Effect of lipophilicity of substituted benzamides on the dopaminergic effects in vivo and in vitro.
    Author: Hall H, Ogren SO, Florvall L.
    Journal: Acta Pharmacol Toxicol (Copenh); 1984 Sep; 55(3):211-5. PubMed ID: 6542298.
    Abstract:
    The antidopaminergic potencies of some new substituted benzamides related to remoxipride have been studied in the rat using in vitro (3H-spiperone binding) and in vivo techniques (antagonism of apomorphine induced stereotypies). The lipophilicities of the different benzamides were calculated by the addition of the lipophilic contribution (pi value) of the added substituent. It was found that the in vivo potencies of the compounds were not direct proportional to the in vitro potencies. The discrepancies in the potencies in vitro and in vivo (expressed as the ratio) are correlated to the calculated lipophilicities. Certain substituents in the benzene nucleus affect this in vitro--in vivo ratio more than could be expected from the change in lipophilicity caused by the substituent. The type of side chain is also of great importance. The reasons for the discrepancies between in vitro and in vivo antidopaminergic potencies of the studied substituted benzamides are discussed.
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