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Morphine glucuronidation increases its analgesic effect in guinea pigs

Title
Morphine glucuronidation increases its analgesic effect in guinea pigs
Type
Article in International Scientific Journal
Year
2014
Authors
Ana Oliveira
(Author)
Other
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Pinho, Dora
(Author)
FMUP
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Albino Teixeira, A
(Author)
FMUP
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Rui Medeiros
(Author)
Other
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Ricardo Jorge Dinis Oliveira
(Author)
FMUP
Felix Carvalho
(Author)
FFUP
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Journal
Title: Life SciencesImported from Authenticus Search for Journal Publications
Vol. 109
Pages: 104-110
ISSN: 0024-3205
Publisher: Elsevier
Scientific classification
FOS: Medical and Health sciences > Other medical sciences
Other information
Authenticus ID: P-009-MS7
Abstract (EN): Aims: Morphine is extensively metabolized to neurotoxic morphine-3-glucuronide (M3G) and opioid agonist morphine-6-glucuronide (M6G). Due to these different roles, interindividual variability and co-administration of drugs that interfere with metabolism may affect analgesia. The aim of the study was to investigate the repercussions of administration of an inducer (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and an inhibitor (ranitidine) of glucuronidation in morphine metabolism and consequent analgesia, using the Guinea pig as a suitable model. Main methods: Thirty male Dunkin-Hartley guinea pigs were divided in six groups: control, morphine, ranitidine, ranitidine + morphine, TCDD and TCDD + morphine. After previous exposure to TCDDand ranitidine, morphine effect was assessed by an increasing temperature hotplate (35-52.5 degrees C), during 60 min after morphine administration. Then, blood was collected and plasma morphine and metabolites were quantified. Key findings: Animals treated with TCDD presented faster analgesic effect and 75% reached the cut-off temperature of 52.5 degrees C, comparing with only 25% in morphine group. Animals treated with ranitidine presented a significantly lower analgesic effect, compared with morphine group (p < 0.05). Moreover, significant differences between groups were found in M3G levels and M3G/morphine ratio (p < 0.001 and p < 0.0001), with TCDD animals presenting the highest values for M3G, M6G, M3G/morphine and M6G/morphine, and the lowest value for morphine. The opposite was observed in the animals treated with ranitidine. Significance: Our results indicate that modulation of morphine metabolism may result in variations in metabolite concentrations, leading to different analgesic responses to morphine, in an animal model that may be used to improve morphine effect in clinical practice.
Language: English
Type (Professor's evaluation): Scientific
Contact: anacorreiadeoliveira@gmail.com; felixdc@ff.up.pt
No. of pages: 7
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