Abstract:
:Drugs may cause serotonin toxicity by a number of different mechanisms including inhibition of serotonin uptake and metabolism, increased serotonin synthesis and release, activation of serotonin receptors, and inhibition of cytochrome P450 oxidases. Some drug interactions involving opioids can increase intrasynaptic levels of serotonin, and opioid analgesic drugs are now recognized as being involved in some cases of serotonin toxicity especially if administered in conjunction with other serotonergic medications including monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants. In March 2016, the FDA issued a Drug Safety Communication concerning the association of the entire class of opioid pain medicines with serotonin toxicity. Reports of the involvement of individual opioids particularly tramadol, tapentadol, meperidine, methadone, oxycodone, fentanyl, and dextromethorphan are reviewed. While relevance to human serotonin toxicity of animal models, including many studies on rat brain synaptosomes, is questionable, important insights have recently been forthcoming from research utilizing 5-HT receptors, serotonin transporter (SERT), and knockout mice. In studies with human SERT-transfected human HEK293 cells, the synthetic opioids tramadol, meperidine, methadone, tapentadol, and dextromethorphan inhibited SERT, but fentanyl and a number of phenanthrenes including morphine and hydromorphone did not. Receptor ligand-binding assays revealed interaction of fentanyl with 5-HT1A receptors and interaction of meperidine, methadone, and fentanyl with 5-HT2A receptors. Although the opioids most often associated with serotonin toxicity in humans inhibit human SERT in vitro, fentanyl and oxycodone are not inhibitory even though their clinical involvement has been reported. This suggests some SERT-independent effects on the serotonin system in vivo. Heightened clinician awareness of the possibility of serotonin toxicity among patients taking opioids and serotonergic antidepressants is called for.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Baldo BAdoi
10.1007/s00204-018-2244-6subject
Has Abstractpub_date
2018-08-01 00:00:00pages
2457-2473issue
8eissn
0340-5761issn
1432-0738pii
10.1007/s00204-018-2244-6journal_volume
92pub_type
杂志文章,评审abstract::Rats were exposed to single periods of inhalation of fumes generated by arc welding. Two processes were compared: either manual metal arc (MMA) using flux-coated mild steel (MS) electrodes or metal inert-gas (MIG) welding with stainless steel (SS). Widespread but small deposits of fume particles were cleared effective...
journal_title:Archives of toxicology
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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