| 词条 | Difelikefalin |
| 释义 |
| Verifiedfields = | Watchedfields = | verifiedrevid = | IUPAC_name = 4-amino-1-[(2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid | image = Difelikefalin.svg | width = 250px | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = | routes_of_administration = Intravenous | bioavailability = 100% (IV)[1] | protein_bound = | metabolism = Not metabolized[1] | elimination_half-life = 2 hours[1] | excretion = Excreted as unchanged drug via bile and urine[1] | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 1024828-77-0 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = NA1U919MRO | KEGG = D11111 | ATC_prefix = None | ATC_suffix = | PubChem = 24794466 | DrugBank_Ref = | DrugBank = | ChemSpiderID_Ref = | ChemSpiderID = 44208824 | C=36 | H=53 | N=7 | O=6 | molecular_weight = 679.85 g/mol | smiles = CC(C)C[C@H](C(=O)N[C@H](CCCCN)C(=O)N1CCC(CC1)(C(=O)O)N)NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@@H](CC3=CC=CC=C3)N | StdInChI = 1S/C36H53N7O6/c1-24(2)21-29(32(45)40-28(15-9-10-18-37)34(47)43-19-16-36(39,17-20-43)35(48)49)42-33(46)30(23-26-13-7-4-8-14-26)41-31(44)27(38)22-25-11-5-3-6-12-25/h3-8,11-14,24,27-30H,9-10,15-23,37-39H2,1-2H3,(H,40,45)(H,41,44)(H,42,46)(H,48,49)/t27-,28-,29-,30-/m1/s1 | StdInChIKey = FWMNVWWHGCHHJJ-SKKKGAJSSA-N | synonyms = }}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[1] acting as a peripherally specific, highly selective agonist of the κ-opioid receptor (KOR).[2][3][4][5] It is under development by Cara Therapeutics as an intravenous agent for the treatment of postoperative pain.[2][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.[2][3] In addition to use as an analgesic, difelikefalin is also being investigated for the treatment of pruritus (itching).[2][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.[2] 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).[2] See also
References1. ^{{cite journal | vauthors = Janecka A, Perlikowska R, Gach K, Wyrebska A, Fichna J | title = Development of opioid peptide analogs for pain relief | journal = Curr. Pharm. Des. | volume = 16 | issue = 9 | pages = 1126–35 | year = 2010 | pmid = 20030621 | doi = 10.2174/138161210790963869| url = }} 2. ^1 2 3 4 5 6 7 8 9 {{cite book|author1=Raymond S. Sinatra|author2=Jonathan S. Jahr|author3=J. Michael Watkins-Pitchford|title=The Essence of Analgesia and Analgesics|url=https://books.google.com/books?id=ZwPIjKg0XukC&pg=PA490|date=14 October 2010|publisher=Cambridge University Press|isbn=978-1-139-49198-3|pages=490–491}} 3. ^1 2 3 4 {{cite book|author=Jeffrey Apfelbaum|title=Ambulatory Anesthesia, An Issue of Anesthesiology Clinics,|url=https://books.google.com/books?id=IlTOAwAAQBAJ&pg=PT190|date=8 September 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-29934-3|pages=190–}} 4. ^1 2 {{cite book|author1=Alan Cowan|author2=Gil Yosipovitch|title=Pharmacology of Itch|url=https://books.google.com/books?id=Jl0SCAAAQBAJ&pg=PA307|date=10 April 2015|publisher=Springer|isbn=978-3-662-44605-8|pages=307–}} 5. ^1 2 3 {{cite book|author=Charlotte Allerton|title=Pain Therapeutics: Current and Future Treatment Paradigms|url=https://books.google.com/books?id=zUINAgAAQBAJ&pg=PA56|year=2013|publisher=Royal Society of Chemistry|isbn=978-1-84973-645-9|pages=56–}} External links
7 : Amines|Antipruritics|Carboxylic acids|Kappa agonists|Opioid peptides|Peripherally selective drugs|Piperidines |
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