Biopharmaceutical profile of tramadol in the dog

摘要

Tramadol (T) is an analgesic opioid drug clinically used since the 1990’s in the relief of mild to moderate pain in humans. The lack of side effects, characteristic of opioid derivatives, shown by this drug, and the absence of typical side effects due to non-steroidal anti-inflammatory drugs, suggest T as a potential molecule for long term therapy of chronic pain in animals. Its analgesic effect is due to a dual mechanism of action: 1) the re-uptake inhibition of norepinephrine and serotonin; 2) agonism of the μ-opioid receptor (the most important mechanism). Such agonism is owed both to the parental drug, then mainly to its metabolite O-demethylated M1 reported as having a 200 fold greater affinity at the μ-receptor. Recently, T has been demonstrated to be metabolized quickly to inactive metabolites, in goats (de Sousa et al. 2008), horses (Giorgi et al. 2007; Shilo et al. 2008) and dogs (Kukanich and Papich 2004; Giorgi et al. 2009) in contrast with cats (Pypendop and Ilkiw 2008) and camels (Elghazali et al. 2008); in these two latter species the M1 metabolite has been detected at high plasma concentrations.