Title | Stereoselective actions of substituted benzamide drugs on cerebral dopamine mechanisms |
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Authors | Jenner, P., Clow, A., Reavill, C., Theodorou, A. and Marsden, C.D. |
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Abstract | Apomorphine-induced locomotor activity in reserpine-pretreated mice was antagonized by pretreatment with (-)-sulpiride and (-)-sultopride. The (+)-enantiomers were inactive. Apomorphine- and amphetamine-induced stereotyped behaviour in rats were antagonized by (-)-sultopride but not by the (+)-enantiomer. Neither enantiomer of sulpiride prevented the onset of the stereotyped response. Both (-)-sulpiride and (-)-sultopride induced increases in striatal and mesolimbic HVA and DOPAC concentrations; (+)-sultopride elevated striatal and mesolimbic DOPAC concentrations but not HVA, while (+)-sulpiride had no effect on HVA or DOPAC in either area. Dopamine concentrations were reduced by the enantiomers of sultopride but not by sulpiride. Low concentrations (10−9 −10−66 M) of the (-)-enantiomers of both drugs displaced [3 H]spiperone from its specific binding site in rat striatal preparations, but the (+)-enantiomers were 40 and 100 times less active. However, neither enantiomer of either drug anatagonized the dopamine-induced stimulation of adenylate cyclase in rat striatal preparations. The data suggest that the central pharmacological activity of sulpiride and sultopride resides in the (-)-enantiomers and that this activity occurs at cerebral dopamine receptors not dependent on adenylate cyclase for functional activity. |
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Journal | Journal of Pharmacy and Pharmacology |
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Journal citation | 32 (1), pp. 39-44 |
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ISSN | 0022-3573 |
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Year | Sep 1980 |
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Publisher | Wiley |
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Digital Object Identifier (DOI) | https://doi.org/10.1111/j.2042-7158.1980.tb12842.x |
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Publication dates |
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Published | Sep 1980 |
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