Tramadol Vs Tapentadol: Anew Horizon in Pain Treatment?

Abstract

Problem statement: Acute and chronic pain is a common presenting sign in animal species and human beings. Approach: Classical opioids provide very effective pain relief, although they may be less effective in the treatment of chronic pain due to their limited therapeutic windows and the induced opioid receptor down regulation. Atypical opioids, such as tramadol and tapentadol, have a dual mechanism of action and have been designed to overcome these issues through an opiate-sparing effect. Results: Tramadol activates mu opioid receptors and in addition, inhibits serotonin and noradrenalin reuptake. These actions are the result of the different enantiomers and tend to be reliant on their metabolism. Indeed, the O-desmethyltramadol phase I metabolite, is 200-300 times more potent for mu opioid receptor activation than the parental compound. For these reasons, the drug's effectiveness can vary among subjects. In veterinary medicine its effectiveness, especially after oral administration, is still uncertain and controversial. Tapentadol is a novel, atypical opioid with a unique mechanism of action. It was launched on the European drug market at the end of 2011. It has been proposed as the first representative of a new pharmacological class of centrally acting analgesics, namely, the mu opioid receptor agonist, noradrenalin reuptake inhibitors. The first human studies describe this molecule as safe and effective (equianalgesic to morphine). The drug has great potential for veterinary use because it exists as a single enantiomer only, it does not require metabolic activation to be effective and adverse effects triggered by the serotonin reuptake inhibition action are negligible. Conclusion/Recommendations: For these reasons, TAP is a promising compound however at this stage, more investigation is required before it can be recommended for regular use in veterinary medicine, the possibility of undesirable effects is yet to be entirely excluded.

Comparative Pharmacology and Toxicology of Tramadol & Tapentadol

“…These metabolites of tramadol are more potent than the parent molecule. Since tramadol needs to be metabolized, it generally has a delayed onset of action and less reliable effect in some individuals 3 .…”

“…However, these drugs were created as effective and yet much safer analogues of morphine. Although both the drugs work by influencing opioid receptors (especially mu-opioid receptors or MOR), there is a difference 3 . Activation of MOR receptors results in the potent painkilling effect of opioids.…”

Mirtazapine in Veterinary Medicine a Pharmacological Rationale for its Application in Chronic Pain

“…It is likely that this is associated with the emergence of peripheral analgesic activity of serotonin when the dose is increased. It has been demonstrated that opioidergic mechanisms are also involved at these two levels (supra spinal and peripheral) (Giorgi, 2012). In contrast, MRZ had no antinociceptive activity at the central spinal level (tail clip and flick tests).…”

“…In canine species, MRZ orally administered (at about 1 mg kg −1 ) showed a favourable pharmacokinetic profile (which is different to that in both cats and humans) compared to other CNS active drugs such as clomipramine (King et al, 2000), fluoxetine (Simpson et al, 2007) and trazodone (Gruen and Sherman, 2008). For these reasons, it was speculated (Giorgi, 2012) to be potentially useful for veterinary patients for treatment of anorexia and a wide range of anxiety-related conditions (Overall, 2000), for its antiemetic properties (due to antagonism of 5-HT 3 receptor) and as an analgesic in chronic and cancerassociated pain, due to its effects on both the noradrenergic and serotonic system (Bannister et al, 2009). Pharmacokinetics and metabolism have been reported to be largely variable among these species.…”