FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2114025861> ?p ?o ?g. }

• W2114025861 abstract "The peripheral endogenous opioid system is critically involved in neuropathic and inflammatory pain generation as suggested by the modulation of opioid receptors expression and enkephalins (ENKs) release observed in these painful conditions. Accordingly, an innovative approach in the treatment of these nocifensive events is to increase and maintain high local concentrations of extracellular pain-evoked ENKs, by preventing their physiological enzymatic inactivation by two Zn metallopeptidases, the neutral endopeptidase (NEP, neprilysin, EC 3.4.24.11) and the neutral aminopeptidase (APN, EC 3.4.11.2). With this aim, new orally active dual ENKephalinase inhibitors (DENKIs) were designed as soluble prodrugs by introducing a N-terminal cleavable carbamate in the previously described aminophosphinic inhibitors. This induces long-lasting antinociceptive responses after oral administration, in various rodent models of inflammatory and neuropathic pain. These responses are mediated through stimulation of peripheral opioid receptors by DENKIs-protected ENKs as demonstrated by naloxone methiodide reversion. In all tested models, the most efficient prodrug 2a (PL265) was active, at least during 150–180 min, after single oral administration of 25–50 mg/kg in mice and of 100–200 mg/kg in rats. In models of neuropathic pain, both hyperalgesia and allodynia were markedly reduced. Interestingly, combination of inactive doses of 2a (PL265) and of the anti-epileptic drug gabapentin had synergistic effect on neuropathic pain. Pharmacokinetic studies of 2a (PL265) in rats show that the active drug is the only generated metabolite produced. These encouraging results have made 2a (PL265) a suitable candidate for clinical development." @default.
• W2114025861 created "2016-06-24" @default.
• W2114025861 creator A5032132304 @default.
• W2114025861 creator A5037897982 @default.
• W2114025861 creator A5051288610 @default.
• W2114025861 creator A5060369838 @default.
• W2114025861 creator A5060645327 @default.
• W2114025861 creator A5068784944 @default.
• W2114025861 date "2015-01-30" @default.
• W2114025861 modified "2023-09-26" @default.
• W2114025861 title "Long‐lasting oral analgesic effects of <i>N</i> ‐protected aminophosphinic dual <scp>ENK</scp> ephalinase inhibitors ( <scp>DENKI</scp> s) in peripherally controlled pain" @default.
• W2114025861 cites W1503834335 @default.
• W2114025861 cites W1768058489 @default.
• W2114025861 cites W1837577432 @default.
• W2114025861 cites W1963627122 @default.
• W2114025861 cites W1964026096 @default.
• W2114025861 cites W1965066118 @default.
• W2114025861 cites W1969109979 @default.
• W2114025861 cites W1975423956 @default.
• W2114025861 cites W1975585602 @default.
• W2114025861 cites W1977704347 @default.
• W2114025861 cites W1978718410 @default.
• W2114025861 cites W1989221461 @default.
• W2114025861 cites W1994374028 @default.
• W2114025861 cites W2005733093 @default.
• W2114025861 cites W2006421982 @default.
• W2114025861 cites W2007270109 @default.
• W2114025861 cites W2011605939 @default.
• W2114025861 cites W2011903568 @default.
• W2114025861 cites W2013144633 @default.
• W2114025861 cites W2025742542 @default.
• W2114025861 cites W2027822995 @default.
• W2114025861 cites W2048166249 @default.
• W2114025861 cites W2048170721 @default.
• W2114025861 cites W2051746492 @default.
• W2114025861 cites W2055514588 @default.
• W2114025861 cites W2058020736 @default.
• W2114025861 cites W2058315281 @default.
• W2114025861 cites W2062379760 @default.
• W2114025861 cites W2064873536 @default.
• W2114025861 cites W2065054369 @default.
• W2114025861 cites W2072446469 @default.
• W2114025861 cites W2074251434 @default.
• W2114025861 cites W2082753783 @default.
• W2114025861 cites W2085573535 @default.
• W2114025861 cites W2094255968 @default.
• W2114025861 cites W2101099825 @default.
• W2114025861 cites W2108240074 @default.
• W2114025861 cites W2116601617 @default.
• W2114025861 cites W2120607548 @default.
• W2114025861 cites W2123281693 @default.
• W2114025861 cites W2125350295 @default.
• W2114025861 cites W2131372228 @default.
• W2114025861 cites W2135539379 @default.
• W2114025861 cites W2148367885 @default.
• W2114025861 cites W2159430466 @default.
• W2114025861 cites W2165157642 @default.
• W2114025861 cites W2166290557 @default.
• W2114025861 cites W2169879202 @default.
• W2114025861 cites W2255934102 @default.
• W2114025861 cites W2260195689 @default.
• W2114025861 cites W2310962972 @default.
• W2114025861 cites W2404849621 @default.
• W2114025861 cites W2416302782 @default.
• W2114025861 doi "https://doi.org/10.1002/prp2.116" @default.
• W2114025861 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4324690" @default.
• W2114025861 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25692029" @default.
• W2114025861 hasPublicationYear "2015" @default.
• W2114025861 type Work @default.
• W2114025861 sameAs 2114025861 @default.
• W2114025861 citedByCount "20" @default.
• W2114025861 countsByYear W21140258612015 @default.
• W2114025861 countsByYear W21140258612016 @default.
• W2114025861 countsByYear W21140258612017 @default.
• W2114025861 countsByYear W21140258612018 @default.
• W2114025861 countsByYear W21140258612019 @default.
• W2114025861 countsByYear W21140258612020 @default.
• W2114025861 countsByYear W21140258612021 @default.
• W2114025861 countsByYear W21140258612022 @default.
• W2114025861 countsByYear W21140258612023 @default.
• W2114025861 crossrefType "journal-article" @default.
• W2114025861 hasAuthorship W2114025861A5032132304 @default.
• W2114025861 hasAuthorship W2114025861A5037897982 @default.
• W2114025861 hasAuthorship W2114025861A5051288610 @default.
• W2114025861 hasAuthorship W2114025861A5060369838 @default.
• W2114025861 hasAuthorship W2114025861A5060645327 @default.
• W2114025861 hasAuthorship W2114025861A5068784944 @default.
• W2114025861 hasBestOaLocation W21140258611 @default.
• W2114025861 hasConcept C104826730 @default.
• W2114025861 hasConcept C126322002 @default.
• W2114025861 hasConcept C142724271 @default.
• W2114025861 hasConcept C15490471 @default.
• W2114025861 hasConcept C170493617 @default.
• W2114025861 hasConcept C181199279 @default.
• W2114025861 hasConcept C185592680 @default.
• W2114025861 hasConcept C204787440 @default.
• W2114025861 hasConcept C2776608144 @default.
• W2114025861 hasConcept C2777107010 @default.
• W2114025861 hasConcept C2777803847 @default.
• W2114025861 hasConcept C2777883359 @default.

• next