Morphine glucuronidation increases its analgesic effect in guinea pigs

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

Ana Oliveira (Autor) Outra; Pinho, Dora (Autor) FMUP; Albino Teixeira, A (Autor) FMUP; Rui Medeiros (Autor) Outra; Ricardo Jorge Dinis Oliveira (Autor) FMUP; Felix Carvalho (Autor) FFUP

Revista

Título: Life Sciences

Vol. 109

Páginas: 104-110

ISSN: 0024-3205

Editora: Elsevier

Indexação

ISI Web of Knowledge - 5 Citações

Scopus - 5 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

Outras Informações

ID Authenticus: P-009-MS7

DOI: 10.1016/j.lfs.2014.06.010

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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7