Mechanistic and functional differentiation of tapentadol and tramadol.
BACKGROUND
Many opioid analgesics share common structural elements; however, minor differences in structure can result in major differences in pharmacological activity, pharmacokinetic profile, and clinical efficacy and tolerability.


METHODS
This review compares and contrasts the chemistry, pharmacodynamics, pharmacokinetics, and CNS 'functional activity' of tapentadol and tramadol, responsible for their individual clinical utilities.


CONCLUSIONS
The distinct properties of tapentadol and tramadol generate different CNS functional activities, making each drug the prototype of different classes of opioid/nonopioid analgesics. Tramadol's analgesia derives from relatively weak µ-opioid receptor (MOR) agonism, plus norepinephrine and serotonin reuptake inhibition, provided collectively by the enantiomers of the parent drug and a metabolite that is a stronger MOR agonist, but has lower CNS penetration. Tapentadol's MOR agonist activity is several-fold greater than tramadol's, with prominent norepinephrine reuptake inhibition and minimal serotonin effect. Accordingly, tramadol is well-suited for pain conditions for which a strong opioid component is not needed-and it has the benefit of a low abuse potential; whereas tapentadol, a schedule-II controlled substance, is well-suited for pain conditions requiring a strong opioid component-and it has the benefit of greater gastrointestinal tolerability compared to classical strong opioids. Both drugs offer distinct and complementary clinical options.
Temple University School of Pharmacy, Department of Pharmaceutical Sciences, Philadelphia, PA, USA.
Robert B
RB
Raffa
Helmut
H
Buschmann
Thomas
T
Christoph
Gary
G
Eichenbaum
Werner
W
Englberger
Christopher M
CM
Flores
Torsten
T
Hertrampf
Babette
B
Kögel
Klaus
K
Schiene
Wolfgang
W
Straßburger
Rolf
R
Terlinden
Thomas M
TM
Tzschentke
D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D010146:Pain / Q000188:drug therapy; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017450:Receptors, Opioid, mu / Q000819:agonists; D000077432:Tapentadol; D014147:Tramadol / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000701:Analgesics, Opioid; D010636:Phenols; D017450:Receptors, Opioid, mu; D014147:Tramadol; D000077432:Tapentadol