The chemical is a derivative of propanoic acid. One use for efaproxiral is to increase the efficacy of certain chemotherapy drugs which have reduced efficacy against hypoxic tumours, and can thus be made more effective by increased offloading of oxygen into the tumour tissues.[4][5][6] No benefit was seen for efaproxiral in phase III clinical trials.[7] The increased oxygenation of tissues could theoretically also produce enhanced exercise capacity in feline, rat and canine models for approximately 100 min. immediately after a high dosage 45 min. intravenous infusion.[8]
This has led World Anti-Doping Agency to categorise efaproxiral under a prohibited method to artificially enhance the uptake, transport or delivery of oxygen.[9] There is no existing evidence that efaproxiral can effectively enhance performance in humans.[10] Efaproxiral can be absorbed via transdermal, rectal, inhalation and gastrointestinal routes, though not at plasma concentrations great enough to alter the oxygen-haemoglobin dissociation curve.[11]
Efaproxiral is explicitly excluded from the 2012 World Anti-Doping Agency list of Prohibited Substances and is explicitly included in the Prohibited Methods section M1 as a forbidden procedure to alter the oxygen-haemoglobin dissociation curve in order to allosterically modify haemoglobin.[12]
Referencesedit
^Farace E, Melikyan Z (2008). "Cognitive Dysfunction, Mood Disorders, and Fatigue". Cancer Neurology in Clinical Practice. pp. 242–248. doi:10.1007/978-1-59745-412-4_7. ISBN978-1-58829-983-3.
^US 5731454, Abraham DJ, Joshi G, Randad R, Panikker J, "Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored blood", issued 24 March 1998, assigned to Virginia Commonwealth University (Richmond, VA).
^Kunert MP, Liard JF, Abraham DJ (August 1996). "RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats". The American Journal of Physiology. 271 (2 Pt 2): H602–H613. doi:10.1152/ajpheart.1996.271.2.H602. PMID 8770102.
^Donnelly ET, Liu Y, Rockwell S (March 2006). "Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors". Experimental Biology and Medicine. 231 (3): 317–321. doi:10.1177/153537020623100312. PMID 16514179. S2CID 19475480.
^Engel RH, Kaklamani VG (April 2006). "Role of efaproxiral in metastatic brain tumors". Expert Review of Anticancer Therapy. 6 (4): 477–485. doi:10.1586/14737140.6.4.477. PMID 16613536. S2CID 3142753.
^Scott C, Suh J, Stea B, Nabid A, Hackman J (December 2007). "Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases". American Journal of Clinical Oncology. 30 (6): 580–587. doi:10.1097/COC.0b013e3180653c0d. PMID 18091051. S2CID 42750048.
^"FDA Advisory Committee Does Not Recommend Approval of RSR13 as Adjunctive Therapy for the Treatment of Brain Metastases Originating from Breast Cancer". Allos Therapeutics, Inc. May 2004 – via Drugs.com.
^Watanabe T, Takeda T, Omiya S, Hikoso S, Yamaguchi O, Nakano Y, et al. (August 2008). "Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure". Journal of the American College of Cardiology. 52 (9): 779–786. doi:10.1016/j.jacc.2008.06.003. PMID 18718428.
^(PDF). World Anti Dopting Agency (WADA). 24 August 2011. Archived from the original (PDF) on 2009-02-03.
^Nóbrega AC (Feb 2002). "RSR13 e modificação alostérica da afinidade hemoglobina-oxigênio: abuso entre atletas" [RSR13 and allosteric change in the hemoglobin-oxygen Afinity [sic]]. Journal of Sports Medicine (in Portuguese). 8. ISSN 1517-8692.
^Campanini B, Raboni M (January 2003). "Oxygen Delivery by Allosteric Effectors of Hemoglobin, Blood Substitutes, and Plasma Expanders". Burger's Medicinal Chemistry, Drug Discovery and Development. pp. 385–441. doi:10.1002/0471266949.bmc048. ISBN978-0471266945.
^(PDF). World Anti Dopting Agency (WADA). 24 August 2011. Archived from the original (PDF) on 2012-05-13. Retrieved 2012-05-10.
February 26, 2024
efaproxiral, analogue, cholesterol, drug, bezafibrate, developed, treatment, depression, traumatic, brain, injury, ischemia, stroke, myocardial, infarction, diabetes, hypoxia, sickle, cell, disease, hypercholesterolemia, radio, sensitiser, clinical, dataatc, c. Efaproxiral INN is an analogue of the cholesterol drug bezafibrate developed for the treatment of depression traumatic brain injury ischemia stroke myocardial infarction diabetes hypoxia sickle cell disease hypercholesterolemia and as a radio sensitiser 1 2 3 EfaproxiralClinical dataATC codeL01XD06 WHO Pharmacokinetic dataElimination half life1 hrIdentifiersIUPAC name 2 4 2 3 5 dimethylphenyl amino 2 oxoethyl phenoxy 2 methylpropanoic acidCAS Number131179 95 8 YPubChem CID122335ChemSpider109085 NUNIIJ81E81G364ChEMBLChEMBL18901 NCompTox Dashboard EPA DTXSID40156934Chemical and physical dataFormulaC 20H 23N O 4Molar mass341 407 g mol 13D model JSmol Interactive imageSMILES Cc1cc cc c1 NC O Cc2ccc cc2 OC C C C O O CInChI InChI 1S C20H23NO4 c1 13 9 14 2 11 16 10 13 21 18 22 12 15 5 7 17 8 6 15 25 20 3 4 19 23 24 h5 11H 12H2 1 4H3 H 21 22 H 23 24 NKey BNFRJXLZYUTIII UHFFFAOYSA N N N Y what is this verify The chemical is a derivative of propanoic acid One use for efaproxiral is to increase the efficacy of certain chemotherapy drugs which have reduced efficacy against hypoxic tumours and can thus be made more effective by increased offloading of oxygen into the tumour tissues 4 5 6 No benefit was seen for efaproxiral in phase III clinical trials 7 The increased oxygenation of tissues could theoretically also produce enhanced exercise capacity in feline rat and canine models for approximately 100 min immediately after a high dosage 45 min intravenous infusion 8 This has led World Anti Doping Agency to categorise efaproxiral under a prohibited method to artificially enhance the uptake transport or delivery of oxygen 9 There is no existing evidence that efaproxiral can effectively enhance performance in humans 10 Efaproxiral can be absorbed via transdermal rectal inhalation and gastrointestinal routes though not at plasma concentrations great enough to alter the oxygen haemoglobin dissociation curve 11 Efaproxiral is explicitly excluded from the 2012 World Anti Doping Agency list of Prohibited Substances and is explicitly included in the Prohibited Methods section M1 as a forbidden procedure to alter the oxygen haemoglobin dissociation curve in order to allosterically modify haemoglobin 12 References edit Farace E Melikyan Z 2008 Cognitive Dysfunction Mood Disorders and Fatigue Cancer Neurology in Clinical Practice pp 242 248 doi 10 1007 978 1 59745 412 4 7 ISBN 978 1 58829 983 3 US 5731454 Abraham DJ Joshi G Randad R Panikker J Allosteric modifiers of hemoglobin useful for decreasing oxygen affinity and preserving oxygen carrying capability of stored blood issued 24 March 1998 assigned to Virginia Commonwealth University Richmond VA Kunert MP Liard JF Abraham DJ August 1996 RSR 13 an allosteric effector of hemoglobin increases systemic and iliac vascular resistance in rats The American Journal of Physiology 271 2 Pt 2 H602 H613 doi 10 1152 ajpheart 1996 271 2 H602 PMID 8770102 Donnelly ET Liu Y Rockwell S March 2006 Efaproxiral RSR13 plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors Experimental Biology and Medicine 231 3 317 321 doi 10 1177 153537020623100312 PMID 16514179 S2CID 19475480 Engel RH Kaklamani VG April 2006 Role of efaproxiral in metastatic brain tumors Expert Review of Anticancer Therapy 6 4 477 485 doi 10 1586 14737140 6 4 477 PMID 16613536 S2CID 3142753 Scott C Suh J Stea B Nabid A Hackman J December 2007 Improved survival quality of life and quality adjusted survival in breast cancer patients treated with efaproxiral Efaproxyn plus whole brain radiation therapy for brain metastases American Journal of Clinical Oncology 30 6 580 587 doi 10 1097 COC 0b013e3180653c0d PMID 18091051 S2CID 42750048 FDA Advisory Committee Does Not Recommend Approval of RSR13 as Adjunctive Therapy for the Treatment of Brain Metastases Originating from Breast Cancer Allos Therapeutics Inc May 2004 via Drugs com Watanabe T Takeda T Omiya S Hikoso S Yamaguchi O Nakano Y et al August 2008 Reduction in hemoglobin oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure Journal of the American College of Cardiology 52 9 779 786 doi 10 1016 j jacc 2008 06 003 PMID 18718428 The 2009 Prohibited List PDF World Anti Dopting Agency WADA 24 August 2011 Archived from the original PDF on 2009 02 03 Nobrega AC Feb 2002 RSR13 e modificacao alosterica da afinidade hemoglobina oxigenio abuso entre atletas RSR13 and allosteric change in the hemoglobin oxygen Afinity sic Journal of Sports Medicine in Portuguese 8 ISSN 1517 8692 Campanini B Raboni M January 2003 Oxygen Delivery by Allosteric Effectors of Hemoglobin Blood Substitutes and Plasma Expanders Burger s Medicinal Chemistry Drug Discovery and Development pp 385 441 doi 10 1002 0471266949 bmc048 ISBN 978 0471266945 The Prohibited List 2012 PDF World Anti Dopting Agency WADA 24 August 2011 Archived from the original PDF on 2012 05 13 Retrieved 2012 05 10 Retrieved from https en wikipedia org w index php title Efaproxiral amp oldid 1168089504, wikipedia, wiki, book, books, library,
