Korean J Pain.  2016 Jul;29(3):153-157. 10.3344/kjp.2016.29.3.153.

Tapentadol: Can It Kill Two Birds with One Stone without Breaking Windows?

• Chang EJ
• Choi EJ
• Kim KH

• KMID: 2327635
• DOI: http://doi.org/10.3344/kjp.2016.29.3.153

Abstract

Tapentadol is a novel oral analgesic with a dual mode of action as an agonist of the µ-opioid receptor (MOR), and as a norepinephrine reuptake inhibitor (NRI) all in a single molecule. Immediate release (IR) tapentadol shows its analgesic effect quickly, at around 30 minutes. Its MOR agonistic action produces acute nociceptive pain relief; its role as an NRI brings about chronic neuropathic pain relief. Absorption is rapid, with a mean maximal serum concentration at 1.25-1.5 h after oral intake. It is present primarily in the form of conjugated metabolites after glucuronidation, and excretes rapidly and completely via the kidneys. The most common adverse reactions are nausea, dizziness, vomiting, and somnolence. Constipation is more common in use of the ER formulation. Precautions against concomitant use of central nervous system depressants, including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol, or use of tapentadol within 14 days of the cessation of monoamine oxidase inhibitors, are advised. The safety and efficacy have not been established for use during pregnancy, labor, and delivery, or for nursing mothers, pediatric patients less than 18 years of age, and cases of severe renal impairment and severe hepatic impairment. The major concerns for tapentadol are abuse, addiction, seeking behavior, withdrawal, and physical dependence. The presumed problem for use of tapentadol is to control the ratio of MOR agonist and NRI. In conclusion, tapentadol produces both nociceptive and neuropathic pain relief, but with worries about abuse and dependence.

Keyword

Acute pain; Addictive behavior; Adverse drug reactions; Alpha adrenergic receptors; Chronic pain; Hyperalgesia; Mode of action; Mu opioid receptor; N-desmethyltapentadol; Neuropathic pain; Nociceptive pain; Tapentadol

MeSH Terms

Absorption
Acute Pain
Analgesics, Opioid
Anesthetics, General
Behavior, Addictive
Birds*
Central Nervous System Depressants
Chronic Pain
Constipation
Dizziness
Drug-Related Side Effects and Adverse Reactions
Humans
Hyperalgesia
Hypnotics and Sedatives
Kidney
Monoamine Oxidase Inhibitors
Mothers
Nausea
Neuralgia
Nociceptive Pain
Norepinephrine
Nursing
Phenothiazines
Pregnancy
Receptors, Adrenergic, alpha
Receptors, Opioid, mu
Vomiting
Analgesics, Opioid
Anesthetics, General
Central Nervous System Depressants
Hypnotics and Sedatives
Monoamine Oxidase Inhibitors
Norepinephrine
Phenothiazines
Receptors, Adrenergic, alpha
Receptors, Opioid, mu

Figure

• 

  Fig. 1 A dual mode of action mechanism for tapentadol. (Modified from Tzschentke TM, Christoph T, Kögel B, Schiene K, Hennies HH, Englberger W, et al. (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther 2007; 323: 265-76. Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 2006; 80: 53-83).

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