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Enhancement of noradrenaline release from rat cerebral cortex by neuroleptic drugs

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Summary

The effect of different neurolepitc drugs (levomepromazine, haloperidol, thioridazine, clozapine and sulpiride) on (−)-3H-noradrenaline uptake and release by parieto-occipital slices of the rat cerebral cortex was investigated.

  1. 1.

    All neuroleptic drugs tested increased the 3H-efflux from electrically stimulated cortical slices preincubated in (−)-3H-noradrenaline already at 1 μM, clozapine was the most potent compound followed by haloperidol, thioridazine, levomepromazine and sulpiride. The enhanced 3H-efflux due to field stimulation was found at concentrations, which did not increase the basal 3H-efflux. Only haloperidol raised the basal 3H-efflux at 1 μM.

  2. 2.

    All neuroleptic drugs failed to inhibit (−)-3H-noradrenaline (10−7M) accumulation by cortical slices at 1 μM. Sulpiride was inactive in concentrations up to 100 μM. Clozapine again proved to be most potent at 10–100 μM.

  3. 3.

    Clozapine was able to enhance the stimulated transmitter overflow when noradrenaline uptake was already blocked by cocaine thus indicating a different mode of action.

  4. 4.

    Clozapine and levomepromazine antagonized the presynaptic α-adrenergic effect of clonidine.

  5. 5.

    The antidepressant drug amitriptyline increased the transmitter efflux at the same concentrations and to a similar extent as neuroleptic agents.

It is concluded that neuroleptics enhance the stimulation induced noradrenaline release mainly by acting on presynaptic α-adrenoceptors. The effect of clozapine, however, includes a noradrenaline uptake inhibition. These findings may explain the increased noradrenaline turnover produced by neuroleptic drugs and the weak antidepressant action of low potent neuroleptics as well.

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Authors and Affiliations

  1. Institut für Pharmakologie, Universität Essen, Hufelandstrasse 55, D-4300, Essen, Federal Republic of Germany

    Gerhard Groß & Hans-Joachim Schümann

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  1. Gerhard Groß
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  2. Hans-Joachim Schümann
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This work was supported by the Deutsche Forschungsgemeinschaft

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Groß, G., Schümann, HJ. Enhancement of noradrenaline release from rat cerebral cortex by neuroleptic drugs. Naunyn-Schmiedeberg's Arch. Pharmacol. 315, 103–109 (1980). https://doi.org/10.1007/BF00499252

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  • DOI: https://doi.org/10.1007/BF00499252

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