| Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice. | |
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MedLine Citation:
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PMID: 19275775 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The serotonin syndrome is a potential side-effect of serotonin-enhancing drugs, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). We recently reported a genetic mouse model for the serotonin syndrome, as serotonin transporter (SERT)-deficient mice have exaggerated serotonin syndrome behavioural responses to the MAOI tranylcypromine and the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP). As numerous case reports implicate the atypical opioids tramadol and meperidine in the development of the human serotonin syndrome, we examined tramadol and meperidine as possible causative drugs in the rodent model of the serotonin syndrome in SERT wild-type (+/+), heterozygous (+/-) and knockout (-/-) mice. Comparisons were made with SERT mice treated with either vehicle or morphine, an opioid not implicated in the serotonin syndrome in humans. Here we show that tramadol and meperidine, but not morphine, induce serotonin syndrome-like behaviours in mice, and we show that this response is exaggerated in mice lacking one or two copies of SERT. The exaggerated response to tramadol in SERT-/- mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635. Further, we show that morphine-, meperidine- and tramadol-induced analgesia is markedly decreased in SERT-/- mice. These studies suggest that caution seems warranted in prescribing or not warning patients receiving SSRIs or MAOIs that dangerous side-effects may occur during concurrent use of tramadol and similar agents. These findings suggest that it is conceivable that there might be increased vulnerability in individuals with SERT polymorphisms that may reduce SERT by more than 50%, the level in SERT+/- mice. |
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Authors:
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Meredith A Fox; Catherine L Jensen; Dennis L Murphy |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2009-03-11 |
Journal Detail:
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Title: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) Volume: 12 ISSN: 1469-5111 ISO Abbreviation: Int. J. Neuropsychopharmacol. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-13 Completed Date: 2009-12-04 Revised Date: 2010-09-07 |
Medline Journal Info:
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Nlm Unique ID: 9815893 Medline TA: Int J Neuropsychopharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1055-65 Citation Subset: IM |
Affiliation:
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Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1264, USA. mfox@mail.nih.gov |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analgesics, Opioid
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pharmacology* Analysis of Variance Animals Behavior, Animal / drug effects* Behavioral Symptoms / genetics* Disease Models, Animal Drug Interactions Drug Synergism Female Meperidine / pharmacology* Mice Mice, Inbred C57BL Mice, Knockout Pain Measurement / drug effects, methods Piperazines / pharmacology Pyridines / pharmacology Serotonin Antagonists / pharmacology Serotonin Plasma Membrane Transport Proteins / deficiency* Tramadol / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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Z01 MH000332-29/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Opioid; 0/Piperazines; 0/Pyridines; 0/Serotonin Antagonists; 0/Serotonin Plasma Membrane Transport Proteins; 146714-97-8/WAY 100635; 27203-92-5/Tramadol; 57-42-1/Meperidine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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