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The Effects of Mirtazapine on the Interactions between Central Noradrenergic and Serotonergic Systems

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Summary

Several lines of evidence have established that antidepressant drug treatments alter the serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) systems. However, very few studies on the interactions between these two systems have been carried out. The characterisation of these interactions seems to be crucial to a better understanding of the mechanism of action of antidepressant drugs.

We have studied the effects of the novel antidepressant mirtazapine (Remeron®, Org 3770) on the interaction between central noradrenergic and serotonergic systems using an in vivo electrophysiological paradigm in the rat. Our results suggest that (±)mirtazapine is an antagonist of both α2-adrenergic auto- and heteroreceptors, whereas (−)mirtazapine is selective for the α2-heteroreceptor and, according to the dose used, can activate terminal serotonin autoreceptors. In view of the important role of α2-adrenoceptors in controlling serotonergic neurotransmission, selective α2-adrenoceptor antagonists with indirect serotonin enhancing effects may represent a new generation of antidepressant drugs.

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References

  1. Blier P, de Montigny C. Chaput Y. A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence. J Clin Psychiatry 1990; 51Suppl.: 14–20

    PubMed  Google Scholar 

  2. Price LH, Charney DS, Delgado PL, et al. Clinical data on the role of serotonin in the mechanism(s) of action of antidepressant drugs. J Clin Psychiatry 1990; 51Suppl.: 44–50

    PubMed  Google Scholar 

  3. Blier P, de Montigny C. Current advances and trends in the treatment of depression. Trends Pharrnacol Sci 1994; 15: 220–6

    Article  CAS  Google Scholar 

  4. Shopsin B, Gershon S, Goldstein M. The use of synthesis inhibitors in defining a role for biogenic amines during imipramine treatment in depressed patients. Psychopharmacol Commun 1975; 1: 239–49

    PubMed  CAS  Google Scholar 

  5. Shopsin B, Friedman E, Gershon S. Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients. Arch Gen Psychiatry 1976; 33: 811–9

    Article  PubMed  CAS  Google Scholar 

  6. Delgado PL, Charney DS, Price LH, et al. Serotonin function and the mechanism of antidepressant action: reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 1990; 47: 411–8

    Article  PubMed  CAS  Google Scholar 

  7. Delgado PL, Miller HL, Salomon RM, et al. The mechanism of antidepressant action in depression [abstract 103.15]. Soc Neurosci 1992; 18: 727

    Google Scholar 

  8. Baraban JM, Aghajanian GK. Suppression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists. Neuropharmacology 1980; 19: 355

    Article  PubMed  CAS  Google Scholar 

  9. Mongeau R, Blier P, de Montigny C. In vivo electrophysiological evidence for a tonic inhibitory action of endogenous noradrenaline on α2-adrenoceptors on 5-hydroxytryptamine terminals in the rat hippocampus. Naunyn Schmiedebergs Arch Pharmacol 1993; 247: 266–72

    Article  Google Scholar 

  10. Chaput Y, Blier P, de Montigny C. In vivo electrophysiological evidence for the regulatory role of autoreceptors on serotonergic terminals. J Neurosci 1986; 6: 2796–801

    PubMed  CAS  Google Scholar 

  11. de Boer T, Nefkens F, Van Helvoirt A. The α2-adrenoreceptor antagonist Org 3770 enhances serotonin transmission in vivo. Eur J Pharmacol 1994; 253: R5–R6

    Article  PubMed  Google Scholar 

  12. Svensson TH, Bunny BS, Aghajanian GK. Inhibition of both NA and 5-HT neurons in brain by the α-adrenergic agonist clonidine. Brain Res 1975; 92: 291–306

    Article  PubMed  CAS  Google Scholar 

  13. Curet O, de Montigny C. Electrophysical characterization of adrenoreceptors in the rat dorsal hippocampus. II. Receptors mediating the effect of synaptically released norepinephrine. Brain Res 1988; 475: 47–57

    Article  PubMed  CAS  Google Scholar 

  14. Blier P, Seletti B, Bouchard C, et al. Functional evidence for the differential responsiveness of pre- and postsynaptic 5-HT1A receptors [abstract]. Soc Neurosci 1994; 20: 632

    Google Scholar 

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Authors and Affiliations

  1. Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Avenue des Pins Ouest, Montréal, Québec, Canada, H3A 1A3

    Claude de Montigny, Nasser Haddjeri, Raymond Mongeau & Pierre Blier

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  1. Claude de Montigny
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  2. Nasser Haddjeri
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  3. Raymond Mongeau
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  4. Pierre Blier
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de Montigny, C., Haddjeri, N., Mongeau, R. et al. The Effects of Mirtazapine on the Interactions between Central Noradrenergic and Serotonergic Systems. CNS Drugs 4 (Suppl 1), 13–17 (1995). https://doi.org/10.2165/00023210-199500041-00004

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  • DOI: https://doi.org/10.2165/00023210-199500041-00004

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