Methadone-induced hypoglycemia Journal Article
| Authors: | Faskowitz, A. J.; Kramskiy, V. N.; Pasternak, G. W. |
| Article Title: | Methadone-induced hypoglycemia |
| Abstract: | To determine if recent observations of hypoglycemia in patients receiving high-dose methadone extended to an animal model, we explored the effects of methadone and other mu-opioids on blood glucose levels in mice. Methadone lowered blood glucose in a dose-dependent manner with 20 mg/kg yielding a nadir in average glucose levels to 55 ± 6 mg/dL from a baseline of 172 ± 7 mg/dL, an effect that was antagonized by naloxone and mu selective antagonists β-funaltrexamine and naloxonazine. The effect was stereoselective and limited to only the l-isomer, while the d-isomer was ineffective. Despite the robust decrease in blood glucose produced by methadone, a series of other mu-opioids, including morphine, fentanyl, levorphanol, oxycodone or morphine-6β-glucuronide failed to lower blood glucose levels. Similar differences among mu-opioid agonists have been observed in other systems, suggesting the possible role of selected splice variants of the mu-opioid receptor gene Oprm1. This mouse model recapitulates our clinical observations and emphasizes the need to carefully monitor glucose levels when using high methadone doses, particularly intravenously, and the need for controlled clinical trials. © 2013 Springer Science+Business Media New York. |
| Keywords: | controlled study; exons; nonhuman; pancreas; mouse; animals; mice; mice, knockout; mus; animal experiment; dose-response relationship, drug; time factors; animalia; hypoglycemia; glucose; blood glucose; methadone; morphine; analgesics, opioid; opioid; mu opiate receptor; receptors, opioid, mu; concentration response; stereochemistry; naloxone; fentanyl; beta funaltrexamine; morphine 6 glucuronide; levorphanol; oxycodone; opioid receptor; isomer; naloxonazine; endocrine |
| Journal Title: | Cellular and Molecular Neurobiology |
| Volume: | 33 |
| Issue: | 4 |
| ISSN: | 0272-4340 |
| Publisher: | Springer |
| Date Published: | 2013-05-01 |
| Start Page: | 537 |
| End Page: | 542 |
| Language: | English |
| DOI: | 10.1007/s10571-013-9919-6 |
| PROVIDER: | scopus |
| PMCID: | PMC3622167 |
| PUBMED: | 23467779 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 June 2013" - "CODEN: CMNED" - "Source: Scopus" |
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