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Comparison of the effects of haloperidol, remoxipride and raclopride on “pre”- and postsynaptic dopamine receptors in the rat brain

Naunyn-Schmiedeberg's Archives of Pharmacology volume 337, pages 379–384 (1988)Cite this article

Summary

The ability of the dopamine receptor antagonists haloperidol, raclopride and remoxipride to prevent the B-HT 920-induced decrease in striatal and limbic L-DOPA accumulation in gamma-butyrolactone (GBL)- and NSD 1015-treated rats (termed ‘GBL-reversal’) was used to define the effects of these compounds on “presynaptic” dopamine receptors. The doses of the dopamine antagonists producing antagonism of GBL-reversal were in each case roughly similar to the doses required to increase dopamine turnover in striatal and limbic areas. The potencies of haloperidol, raclopride and remoxipride in the GBL model were compared with their potencies in behavioural models for postsynaptic dopamine receptors. Haloperidol produced antagonism of GBL-reversal over a similar dose range to that required for antagonism of apomorphine-induced hyperactivity and stereotypy syndromes. Raclopride was effective in the order of potency: antagonism of apomorphine-induced hyperactivity > antagonism of GBL-reversal > antagonism of apomorphine-induced stereotypy. For remoxipride, the dose-response curve for antagonism of GBL-reversal was superimposable over that for antagonism of apomorphine-induced stereotypies, with an ED50 value about 12 times higher than that for antagonism of apomorphine-induced hyperactivity. Thus, the relative potencies of dopamine receptor antagonists at “pre-” and postsynaptic dopamine receptors vary considerably from compound to compound.

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Affiliations

  1. Research and Development Laboratories, Astra Alab AB, S-15185, Södertälje, Sweden

    Olle Magnusson, Christopher J. Fowler, Bodil Mohringe, Agneta Wijkström & Sven-Ove Ögren

  2. Department of Geriatric Medicine, Karolinska Institutet, Huddinge Sjukhus, S-14186, Huddinge, Sweden

    Christopher J. Fowler

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  1. Olle Magnusson
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  2. Christopher J. Fowler
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  3. Bodil Mohringe
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  4. Agneta Wijkström
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  5. Sven-Ove Ögren
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Magnusson, O., Fowler, C.J., Mohringe, B. et al. Comparison of the effects of haloperidol, remoxipride and raclopride on “pre”- and postsynaptic dopamine receptors in the rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 337, 379–384 (1988). https://doi.org/10.1007/BF00169527

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  • DOI: https://doi.org/10.1007/BF00169527

Key words

  • Dopamine receptors
  • Gamma-butyrolactone
  • Haloperidol
  • Raclopride
  • Remoxipride