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Comparison of the effects of mianserin and its enantiomers and metabolites on a behavioral screen for antidepressant activity

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Abstract

The behavioral effects of racemic mianserin, its (+) and (−) enantiomers, and its metabolites desmethylmianserin and 8-hydroxymianserin were evaluated on the differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule, a screen known to be sensitive to and specific for the antidepressant properties of drugs. Racemic mianserin produced the antidepressant-like effect (increased reinforcement rate, decreased response rate) at 5 and 10 mg/kg. The mianserin enantiomers showed the antidepressant-like effect beginning at lower doses [(+) mianserin; 0.6 mg/kg; (−) mianserin: 2.5 mg/kg]. The mianserin metabolites showed no clear dose-related effect at doses up to 10 mg/kg. It is concluded that the antidepressant-like effects of mianserin are due to the activity of the parent compound rather than to its metabolites, and that they may be primarily attributable to the (+) enantiomer. The greater potency of (+)-mianserin may be related to its higher affinity for the 5-HT2 receptor.

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Author notes

  1. Timothy H. Hand

    Present address: Department of Psychology, Oglethorpe University, 30319, Atlanta, GA, USA

  2. Gerard J. Marek

    Present address: Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 06514, New Haven, CT, USA

Authors and Affiliations

  1. Department of Pharmacological and Physiological Sciences, The University of Chicago, 947 East 58th Street, 60637, Chicago, IL, USA

    Timothy H. Hand, Gerard J. Marek & Lewis S. Seiden

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  1. Timothy H. Hand
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  2. Gerard J. Marek
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  3. Lewis S. Seiden
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Hand, T.H., Marek, G.J. & Seiden, L.S. Comparison of the effects of mianserin and its enantiomers and metabolites on a behavioral screen for antidepressant activity. Psychopharmacology 105, 453–458 (1991). https://doi.org/10.1007/BF02244363

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  • DOI: https://doi.org/10.1007/BF02244363

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