Abstract
The antidepressant mirtazapine is an optically active drug and currently marketed as a racemic compound consisting of its S(+) and R(-)-enantiomers in a 50:50 mixture. As stereochemistry of antidepressants has become increasingly important to consider for the relevance of their analgesic properties, we investigated the effect of (+/-)-mirtazapine and its enantiomers in an animal model of acute thermal nociception. Wistar rats were injected intrathecal with either (+/-)-mirtazapine, R(-)-mirtazapine, S(+)-mirtazapine from 1 to 0.001 mg/kg and vehicle (0.9% NaCl), respectively. The effects on thermal paw withdrawal thresholds were monitored using the Hargreaves test. (+/-)-Mirtazapine exerted pro- and antinociceptive effects in acute thermal nociception, whereas R(-)-mirtazapine showed solely antinociceptive and S(+)-mirtazapine pronociceptive properties. These results clearly demonstrate a differential effect of (+/-)-mirtazapine and its enantiomers on nociception. As R(-)-mirtazapine exerts the antinociceptive activity of the racemic mixture it may be a putative candidate for an enantioselective use as analgesic.
References
Sep 1, 1979·Archives of General Psychiatry·A P Zis, F K Goodwin
Jan 1, 1988·Pain·K HargreavesJ Joris
Apr 1, 1988·Neuropharmacology·T H de BoerR M Pinder
Dec 1, 1995·International Clinical Psychopharmacology·N HaddjeriC de Montigny
Dec 1, 1995·International Clinical Psychopharmacology·T de Boer
Dec 1, 1996·Pain·H J McQuayR A Moore
Jun 1, 1997·British Journal of Pharmacology·J T LiebelH U Zeilhofer
Apr 1, 1997·The Journal of Pharmacy and Pharmacology·J KelderV Nickolson
Oct 17, 1998·European Journal of Pharmacology·C McGrathT R Norman
Mar 5, 1999·Journal of Psychopharmacology·A J Smith
Sep 4, 2001·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·H Ueda, M Inoue
Apr 5, 2002·Journal of Molecular Neuroscience : MN·Shaul SchreiberChaim G Pick
Oct 10, 2002·Brain Research Bulletin·Shaul SchreiberChaim G Pick
Oct 31, 2002·Human Psychopharmacology·Seetal DoddTrevor R. Norman
Jan 15, 2003·Current Pain and Headache Reports·Lori Reisner
Jun 28, 2003·Science·Seifollah AhmadiHanns Ulrich Zeilhofer
Nov 19, 2003·Spine·Thomas O StaigerRichard A Deyo
May 18, 2004·Neurochemistry International·Julie Wieseler-FrankLinda R Watkins
Aug 27, 2004·Anesthesiology·Uta Muth-SelbachHanns Ulrich Zeilhofer
Feb 8, 2005·Neuropharmacology·Signe F BomholtGordon Blackburn-Munro
Jun 7, 2005·Expert Opinion on Pharmacotherapy·Armin Szegedi, Natascha Schwertfeger
Jul 30, 2005·Neurochemistry International·Aya NitandaHiroaki Nishio
Citations
Jul 10, 2013·Neurochemical Research·Xiaoyu LiuJianguo Xu
Jan 24, 2009·Brain Research Bulletin·Uta Muth-SelbachRainer Freynhagen
Aug 26, 2014·Psychopharmacology·Michael PaulzenSarah E Groppe
Mar 3, 2007·Clinical Pharmacology and Therapeutics·J BrockmöllerJ Kirchheiner
Jul 19, 2008·Anesthesia and Analgesia·Michael J Sheen, Shung-Tai Ho
Mar 2, 2019·Neurological Research·Ezgi BekturOzgur Devrim Can
Oct 30, 2020·Organic & Biomolecular Chemistry·Srinivas ChamakuriDamian W Young