Systematic (IUPAC) name
4-Amino-1-(D-phenylalanyl-D-phenylalanyl-D-leucyl-D-lysyl)piperidine-4-carboxylic acid
Clinical data
Routes of
Pharmacokinetic data
Bioavailability 100% (IV)[1]
Metabolism Not metabolized[1]
Biological half-life 2 hours[1]
Excretion Excreted as unchanged
drug via bile and urine[1]
CAS Registry Number
ATC code None
Chemical data
Formula C36H53N7O6
Molecular mass 679.85 g/mol

Difelikefalin (INN) (developmental code names CR845, FE-202845), also known as D-Phe-D-Phe-D-Leu-D-Lys-[γ-(4-N-piperidinyl)amino carboxylic acid] (as the acetate salt), is an analgesic opioid peptide[2] acting as a peripherally-specific, highly selective agonist of the κ-opioid receptor (KOR).[1][3][4][5] It is under development by Cara Therapeutics as an intravenous agent for the treatment of postoperative pain.[1][3][5] An oral formulation has also been developed.[5] Due to its peripheral selectivity, difelikefalin lacks the central side effects like sedation, dysphoria, and hallucinations of previous KOR-acting analgesics such as pentazocine and phenazocine.[1][3] In addition to use as an analgesic, difelikefalin is also being investigated for the treatment of pruritus (itching).[1][3][4] Difelikefalin has completed phase II clinical trials for postoperative pain and has demonstrated significant and "robust" clinical efficacy, along with being safe and well-tolerated.[3][5] It is also in phase II clinical trials for uremic pruritus in hemodialysis patients.[4]

Difelikefalin acts as an analgesic by activating KORs on peripheral nerve terminals and KORs expressed by certain immune system cells.[1] Activation of KORs on peripheral nerve terminals results in the inhibition of ion channels responsible for afferent nerve activity, causing reduced transmission of pain signals, while activation of KORs expressed by immune system cells results in reduced release of proinflammatory, nerve-sensitizing mediators (e.g., prostaglandins).[1]

See also


  1. ^ a b c d e f g h i j Raymond S. Sinatra; Jonathan S. Jahr; J. Michael Watkins-Pitchford (14 October 2010). The Essence of Analgesia and Analgesics. Cambridge University Press. pp. 490–491.  
  2. ^ Janecka A, Perlikowska R, Gach K, Wyrebska A, Fichna J (2010). "Development of opioid peptide analogs for pain relief". Curr. Pharm. Des. 16 (9): 1126–35.  
  3. ^ a b c d e Jeffrey Apfelbaum (8 September 2014). Ambulatory Anesthesia, An Issue of Anesthesiology Clinics,. Elsevier Health Sciences. pp. 190–.  
  4. ^ a b c Alan Cowan; Gil Yosipovitch (10 April 2015). Pharmacology of Itch. Springer. pp. 307–.  
  5. ^ a b c d Charlotte Allerton (2013). Pain Therapeutics: Current and Future Treatment Paradigms. Royal Society of Chemistry. pp. 56–.  

External links

  • CR845 - Cara Therapeutics
  • CR845 - AdisInsight