FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2979696989> ?p ?o ?g. }

• W2979696989 endingPage "236" @default.
• W2979696989 startingPage "224" @default.
• W2979696989 abstract "Agonists at the <i>δ</i> opioid receptor are known to be potent antihyperalgesics in chronic pain models and effective in models of anxiety and depression. However, some <i>δ</i> opioid agonists have proconvulsant properties while tolerance to the therapeutic effects can develop. Previous evidence indicates that different agonists acting at the <i>δ</i> opioid receptor differentially engage signaling and regulatory pathways with significant effects on behavioral outcomes. As such, interest is now growing in the development of biased agonists as a potential means to target specific signaling pathways and potentially improve the therapeutic profile of <i>δ</i> opioid agonists. Here, we report on PN6047 (3-[[4-(dimethylcarbamoyl)phenyl]-[1-(thiazol-5-ylmethyl)-4-piperidylidene]methyl]benzamide), a novel G protein–biased and selective <i>δ</i> opioid agonist. In cell-based assays, PN6047 fully engages G protein signaling but is a partial agonist in both the arrestin recruitment and internalization assays. PN6047 is effective in rodent models of chronic pain but shows no detectable analgesic tolerance following prolonged treatment. In addition, PN6047 exhibited antidepressant-like activity in the forced swim test, and importantly, the drug had no effect on chemically induced seizures. PN6047 did not exhibit reward-like properties in the conditioned place preference test or induce respiratory depression. Thus, <i>δ</i> opioid ligands with limited arrestin signaling such as PN6047 may be therapeutically beneficial in the treatment of chronic pain states. <h3>SIGNIFICANCE STATEMENT</h3> PN6047 (3-[[4-(dimethylcarbamoyl)phenyl]-[1-(thiazol-5-ylmethyl)-4-piperidylidene]methyl]benzamide) is a selective, G protein–biased <i>δ</i> opioid agonist with efficacy in preclinical models of chronic pain. No analgesic tolerance was observed after prolonged treatment, and PN6047 does not display proconvulsant activity or other opioid-mediated adverse effects. Our data suggest that <i>δ</i> opioid ligands with limited arrestin signaling will be beneficial in the treatment of chronic pain." @default.
• W2979696989 created "2019-10-18" @default.
• W2979696989 creator A5024658036 @default.
• W2979696989 creator A5028475506 @default.
• W2979696989 creator A5032154770 @default.
• W2979696989 creator A5037505662 @default.
• W2979696989 creator A5037712558 @default.
• W2979696989 creator A5044097175 @default.
• W2979696989 creator A5053765063 @default.
• W2979696989 creator A5058981376 @default.
• W2979696989 creator A5070087115 @default.
• W2979696989 creator A5076467973 @default.
• W2979696989 creator A5082025917 @default.
• W2979696989 creator A5085499871 @default.
• W2979696989 creator A5087403435 @default.
• W2979696989 date "2019-10-08" @default.
• W2979696989 modified "2023-09-30" @default.
• W2979696989 title "A Novel G Protein–Biased Agonist at the <i>δ</i> Opioid Receptor with Analgesic Efficacy in Models of Chronic Pain" @default.
• W2979696989 cites W138314167 @default.
• W2979696989 cites W1505180011 @default.
• W2979696989 cites W1738288880 @default.
• W2979696989 cites W1927614137 @default.
• W2979696989 cites W1975585602 @default.
• W2979696989 cites W1978654075 @default.
• W2979696989 cites W1998654972 @default.
• W2979696989 cites W1998943190 @default.
• W2979696989 cites W2003717081 @default.
• W2979696989 cites W2005492665 @default.
• W2979696989 cites W2006803138 @default.
• W2979696989 cites W2010469304 @default.
• W2979696989 cites W2012192563 @default.
• W2979696989 cites W2012966353 @default.
• W2979696989 cites W2014790939 @default.
• W2979696989 cites W2026601485 @default.
• W2979696989 cites W2052033071 @default.
• W2979696989 cites W2053855385 @default.
• W2979696989 cites W2058068808 @default.
• W2979696989 cites W2062897333 @default.
• W2979696989 cites W2067924690 @default.
• W2979696989 cites W2072807884 @default.
• W2979696989 cites W2076790897 @default.
• W2979696989 cites W2083136363 @default.
• W2979696989 cites W2085937704 @default.
• W2979696989 cites W2086028888 @default.
• W2979696989 cites W2087575237 @default.
• W2979696989 cites W2126041445 @default.
• W2979696989 cites W2143201938 @default.
• W2979696989 cites W2146239445 @default.
• W2979696989 cites W2163468546 @default.
• W2979696989 cites W2164041316 @default.
• W2979696989 cites W2223515559 @default.
• W2979696989 cites W2304807111 @default.
• W2979696989 cites W2324496045 @default.
• W2979696989 cites W2466837313 @default.
• W2979696989 cites W2792285367 @default.
• W2979696989 cites W2794587166 @default.
• W2979696989 cites W2799895587 @default.
• W2979696989 cites W2911664002 @default.
• W2979696989 cites W4232953463 @default.
• W2979696989 doi "https://doi.org/10.1124/jpet.119.258640" @default.
• W2979696989 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6978697" @default.
• W2979696989 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31594792" @default.
• W2979696989 hasPublicationYear "2019" @default.
• W2979696989 type Work @default.
• W2979696989 sameAs 2979696989 @default.
• W2979696989 citedByCount "36" @default.
• W2979696989 countsByYear W29796969892020 @default.
• W2979696989 countsByYear W29796969892021 @default.
• W2979696989 countsByYear W29796969892022 @default.
• W2979696989 countsByYear W29796969892023 @default.
• W2979696989 crossrefType "journal-article" @default.
• W2979696989 hasAuthorship W2979696989A5024658036 @default.
• W2979696989 hasAuthorship W2979696989A5028475506 @default.
• W2979696989 hasAuthorship W2979696989A5032154770 @default.
• W2979696989 hasAuthorship W2979696989A5037505662 @default.
• W2979696989 hasAuthorship W2979696989A5037712558 @default.
• W2979696989 hasAuthorship W2979696989A5044097175 @default.
• W2979696989 hasAuthorship W2979696989A5053765063 @default.
• W2979696989 hasAuthorship W2979696989A5058981376 @default.
• W2979696989 hasAuthorship W2979696989A5070087115 @default.
• W2979696989 hasAuthorship W2979696989A5076467973 @default.
• W2979696989 hasAuthorship W2979696989A5082025917 @default.
• W2979696989 hasAuthorship W2979696989A5085499871 @default.
• W2979696989 hasAuthorship W2979696989A5087403435 @default.
• W2979696989 hasBestOaLocation W29796969891 @default.
• W2979696989 hasConcept C118552586 @default.
• W2979696989 hasConcept C126322002 @default.
• W2979696989 hasConcept C135285700 @default.
• W2979696989 hasConcept C14397066 @default.
• W2979696989 hasConcept C170493617 @default.
• W2979696989 hasConcept C185592680 @default.
• W2979696989 hasConcept C2777389121 @default.
• W2979696989 hasConcept C2777503648 @default.
• W2979696989 hasConcept C2778938600 @default.
• W2979696989 hasConcept C2780231548 @default.
• W2979696989 hasConcept C2780820201 @default.
• W2979696989 hasConcept C2781063702 @default.
• W2979696989 hasConcept C2781118164 @default.

• next