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Effects of DU 24565 (6-nitroquipazine) on serotoninergic and noradrenergic neurones of the rat brain and comparison with the effects of quipazine

Naunyn-Schmiedeberg's Archives of Pharmacology volume 326, pages 198–202 (1984)Cite this article

Summary

Rat brain cortex slices were prepared in order to study the influence of DU 24565 (6-nitroquipazine) and quipazine on the accumulation of tritium, and to investigate the effects of DU 24565 on the electrically evoked (3 Hz) tritium overflow from slices preincubated with 3H-serotonin (3H-5-HT) or 3H-noradrenaline (3H-NA). The influence of DU 24565 and quipazine on the activity of MAO was studied in rat brain homogenates, using labelled serotonin as a substrate.

  1. 1.

    In cortex slices preincubated with either 3H-5-HT or 3H-NA, DU 24565 increased the electrically evoked 3H overflow (higher potency in slices preincubated with 3H-5-HT; the percentage of 3H accounted for by unmetabolized 3H-5-HT was also increased). The facilitatory effects of DU 24565 on evoked 3H overflow were abolished when the respective monoamine uptake mechanisms had previously been blocked by citalopram and cocaine, respectively.

  2. 2.

    The inhibitory effects of unlabelled 5-HT and NA on the evoked 3H overflow from cortex slices preincubated with 3H-5-HT were not altered by DU 24565. Similarly, the drug did not affect the inhibition by NA of the evoked 3H overflow from cortex slices preincubated with 3H-NA.

  3. 3.

    Quipazine was a weak and non-selective inhibitor of the accumulation of 3H-5-HT and 3H-NA. DU 24565 was about 65 times more potent and about 1100 times more selective than quipazine as an inhibitor of 3H-5-HT accumulation, and it was also superior to citalopram and paroxetine in this respect.

  4. 4.

    DU 24565 and quipazine inhibited MAO activity of rat brain homogenates with low potency, DU 24565 being 4–5 times less potent than its parent compound.

It is concluded that DU 24565 (unlike quipazine) is not an antagonist at 5-HT autoreceptors nor at the α2-adrenoceptors on the serotoninergic and noradrenergic neurones of rat brain cortex. Due to its high potency and selectivity as a neuronal 5-HT uptake inhibitor, DU 24565 is a suitable tool for in vitro studies of serotonin release (optimal DU 24565 concentration for this purpose: 1 μmol/l).

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Affiliations

  1. Pharmakologisches Institut der Universität Essen, Hufelandstrasse 55, D-4300, Essen 1, Federal Republic of Germany

    Karin Classen, Manfred Göthert & Eberhard Schlicker

Authors
  1. Karin Classen
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  2. Manfred Göthert
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  3. Eberhard Schlicker
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This study was supported by a grant of the Deutsche Forschungsgemeinschaft

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Classen, K., Göthert, M. & Schlicker, E. Effects of DU 24565 (6-nitroquipazine) on serotoninergic and noradrenergic neurones of the rat brain and comparison with the effects of quipazine. Naunyn-Schmiedeberg's Arch. Pharmacol. 326, 198–202 (1984). https://doi.org/10.1007/BF00505318

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  • DOI: https://doi.org/10.1007/BF00505318

Key words

  • DU 24565
  • Quipazine
  • Serotonin uptake
  • Serotonin release
  • Presynaptic receptors