Mirtazapine and its enantiomers differentially modulate acute thermal nociception in rats.
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.
Klinik für Anaesthesiologie, Moorenstrasse 5, Universitätsklinikum Düsseldorf, D-40225 Düsseldorf, Germany.
Rainer
R
Freynhagen
Jennifer
J
Vogt
Peter
P
Lipfert
Uta
U
Muth-Selbach
D000344:Afferent Pathways / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D006358:Hot Temperature / Q000009:adverse effects; D007278:Injections, Spinal; D007536:Isomerism; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000078785:Mirtazapine; D008968:Molecular Conformation; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013697:Thermosensing / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine