Korean J Pain.  2018 Apr;31(2):73-79. 10.3344/kjp.2018.31.2.73.

Can oliceridine (TRV130), an ideal novel µ receptor G protein pathway selective (µ-GPS) modulator, provide analgesia without opioid-related adverse reactions?

• Ok HG
• Kim SY
• Lee SJ
• Kim TK
• Huh BK
• Kim KH

• KMID: 2410828
• DOI: http://doi.org/10.3344/kjp.2018.31.2.73

Abstract

All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to µ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the β-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the β-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the µ receptor G protein pathway selective (µ-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased µ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.

Keyword

Adverse drug reactions; Beta-arrestin 2; G protein-coupled receptors; Intracellular signaling peptides and proteins; Knockout mice; Ligands; Mu opioid receptor; Oliceridine; Opioid analgesics; Patient safety

MeSH Terms

Analgesia
Analgesics, Opioid
Animals
Bias (Epidemiology)
Drug-Related Side Effects and Adverse Reactions
GTP-Binding Proteins*
Intracellular Signaling Peptides and Proteins
Ligands
Mice
Mice, Knockout
Nausea
Patient Safety
Pharmacokinetics
Receptors, Opioid
Receptors, Opioid, mu
Respiratory Insufficiency
Vomiting
Analgesics, Opioid
GTP-Binding Proteins
Intracellular Signaling Peptides and Proteins
Ligands
Receptors, Opioid
Receptors, Opioid, mu