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Search: (WFRF:(Sundin Anders)) srt2:(2020-2024) > Paracetamol analogu...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006885naa a2200577 4500
001oai:lup.lub.lu.se:d3cc82cb-5385-430e-ae51-f3dac5c1af30
003SwePub
008210111s2021 | |||||||||||000 ||eng|
009oai:DiVA.org:liu-175088
0247 a https://lup.lub.lu.se/record/d3cc82cb-5385-430e-ae51-f3dac5c1af302 URI
0247 a https://doi.org/10.1016/j.ejmech.2020.1130422 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1750882 URI
040 a (SwePub)lud (SwePub)liu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Nilsson, Johanu Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ, Sweden4 aut0 (Swepub:lu)med-jn3
2451 0a Paracetamol analogues conjugated by FAAH induce TRPV1-mediated antinociception without causing acute liver toxicity
264 1b Elsevier BV,c 2021
500 a Funding Agencies|Medical Faculty of Lund University [ALFSKANE-450751]; AFA Forsakring [140376]; Hjarnfonden [FO2019-0316]; Stiftelsen Olle Engkvist ByggmastareSwedish Research Council [189-290]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [07879]; Royal Physiographic Society, Lund Sweden; Clermont Auvergne University, INSERM; Agence Nationale de la Recherche of the French government through the program "Investissements dAvenir (I-Site CAP 20-25)French National Research Agency (ANR)
520 a Paracetamol, one of the most widely used pain-relieving drugs, is deacetylated to 4-aminophenol (4-AP) that undergoes fatty acid amide hydrolase (FAAH)-dependent biotransformation into N-arachidonoylphenolamine (AM404), which mediates TRPV1-dependent antinociception in the brain of rodents. However, paracetamol is also converted to the liver-toxic metabolite N-acetyl-p-benzoquinone imine already at therapeutic doses, urging for safer paracetamol analogues. Primary amine analogues with chemical structures similar to paracetamol were evaluated for their propensity to undergo FAAH-dependent N-arachidonoyl conjugation into TRPV1 activators both in vitro and in vivo in rodents. The antinociceptive and antipyretic activity of paracetamol and primary amine analogues was examined with regard to FAAH and TRPV1 as well as if these analogues produced acute liver toxicity. 5-Amino-2-methoxyphenol (2) and 5-aminoindazole (3) displayed efficient target protein interactions with a dose-dependent antinociceptive effect in the mice formalin test, which in the second phase was dependent on FAAH and TRPV1. No hepatotoxicity of the FAAH substrates transformed into TRPV1 activators was observed. While paracetamol attenuates pyrexia via inhibition of brain cyclooxygenase, its antinociceptive FAAH substrate 4-AP was not antipyretic, suggesting separate mechanisms for the antipyretic and antinociceptive effect of paracetamol. Furthermore, compound 3 reduced fever without a brain cyclooxygenase inhibitory action. The data support our view that analgesics and antipyretics without liver toxicity can be derived from paracetamol. Thus, research into the molecular actions of paracetamol could pave the way for the discovery of analgesics and antipyretics with a better benefit-to-risk ratio.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmakologi och toxikologi0 (SwePub)301022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmacology and Toxicology0 (SwePub)301022 hsv//eng
653 a Acetaminophen
653 a Analgesic
653 a FAAH
653 a Fever
653 a Pain
653 a Paracetamol
653 a TRP channel
653 a TRPV1
653 a Paracetamol; Acetaminophen; TRP channel; TRPV1; FAAH; Analgesic; Pain; Fever
7001 a Mallet, Christopheu ANALGESIA Institute,University of Auvergne,Univ Clermont Auvergne, France; ANALGESIA Inst, France4 aut
7001 a Shionoya, Kisekou Linköpings universitet,Linköping University,Avdelningen för neurobiologi,Medicinska fakulteten4 aut0 (Swepub:liu)kissh42
7001 a Blomgren, Andersu Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ, Sweden4 aut0 (Swepub:lu)med-abl
7001 a Sundin, Anders P.u Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,Lund Univ, Sweden4 aut0 (Swepub:lu)ok2-aps
7001 a Grundemar, Larsu Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ, Sweden4 aut0 (Swepub:lu)med-lgd
7001 a Boudieu, Ludivineu University of Auvergne,ANALGESIA Institute,Univ Clermont Auvergne, France; ANALGESIA Inst, France4 aut
7001 a Blomqvist, Anders,d 1949-u Linköpings universitet,Linköping University,Medicinska fakulteten,Avdelningen för neurobiologi4 aut0 (Swepub:liu)andbl47
7001 a Eschalier, Alainu University of Auvergne,ANALGESIA Institute,Univ Clermont Auvergne, France; ANALGESIA Inst, France4 aut
7001 a Nilsson, Ulf J.u Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH4 aut0 (Swepub:lu)ok2-uni
7001 a Zygmunt, Peter M.u Lund University,Lunds universitet,Neurofarmakologi och smärta,Forskargrupper vid Lunds universitet,Neuropharmacology and pain,Lund University Research Groups,Lund Univ, Sweden4 aut0 (Swepub:lu)kfar-pzy
7102 a Avdelningen för klinisk kemi och farmakologib Institutionen för laboratoriemedicin4 org
7730 t European Journal of Medicinal Chemistryd : Elsevier BVg 213q 213x 0223-5234x 1768-3254
8564 u http://dx.doi.org/10.1016/j.ejmech.2020.113042x freey FULLTEXT
8564 u https://doi.org/10.1016/j.ejmech.2020.113042
8564 u https://liu.diva-portal.org/smash/get/diva2:1546069/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://lup.lub.lu.se/record/d3cc82cb-5385-430e-ae51-f3dac5c1af30
8564 8u https://doi.org/10.1016/j.ejmech.2020.113042
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-175088

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