dc.contributor.author
Gonzalez-Rodriguez, Sara
dc.contributor.author
Quadir, Mohiuddin A.
dc.contributor.author
Gupta, Shilpi
dc.contributor.author
Walker, Karolina A.
dc.contributor.author
Zhang, Xuejiao
dc.contributor.author
Spahn, Viola
dc.contributor.author
Labuz, Dominika
dc.contributor.author
Rodriguez-Gaztelumendi, Antonio
dc.contributor.author
Schmelz, Martin
dc.contributor.author
Joseph, Jan
dc.contributor.author
Parr, Maria K.
dc.contributor.author
Machelska, Halina
dc.contributor.author
Haag, Rainer
dc.contributor.author
Stein, Christoph
dc.date.accessioned
2018-06-08T10:47:28Z
dc.date.available
2017-08-28T08:33:57.282Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21088
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24385
dc.description.abstract
Novel painkillers are urgently needed. The activation of opioid receptors in
peripheral inflamed tissue can reduce pain without central adverse effects
such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy
and report the synthesis and analgesic efficacy of the standard opioid
morphine covalently attached to hyperbranched polyglycerol (PG-M) by a
cleavable linker. With its high-molecular weight and hydrophilicity, this
conjugate is designed to selectively release morphine in injured tissue and to
prevent blood-brain barrier permeation. In contrast to conventional morphine,
intravenous PG-M exclusively activated peripheral opioid receptors to produce
analgesia in inflamed rat paws without major side effects such as sedation or
constipation. Concentrations of morphine in the brain, blood, paw tissue, and
in vitro confirmed the selective release of morphine in the inflamed milieu.
Thus, PG-M may serve as prototype of a peripherally restricted opioid
formulation designed to forego central and intestinal side effects.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie
dc.title
Polyglycerol-opioid conjugate produces analgesia devoid of side effects
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
eLife. - (2017), 6, Artikel Nr. e27081
dcterms.bibliographicCitation.doi
10.7554/eLife.27081
dcterms.bibliographicCitation.url
http://doi.org/10.7554/eLife.27081.001
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.mycore.fudocsId
FUDOCS_document_000000027670
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008648
dcterms.accessRights.openaire
open access