Matches in SemOpenAlex for { <https://semopenalex.org/work/W2045131433> ?p ?o ?g. }
Showing items 1 to 78 of
78
with 100 items per page.
- W2045131433 endingPage "S33" @default.
- W2045131433 startingPage "S33" @default.
- W2045131433 abstract "Chronic pain is inadequately managed with currently available analgesic drug classes (opioids, NSAIDs, adjuvants). A great deal of emphasis has been placed on identifying novel molecular targets for analgesics. Potential novel targets include specific subtypes of nicotinic acetylcholine receptors (nAChRs). Efforts have focused on antagonists acting primarily on subtypes such as α4β2 and α7 nAChRs. Recent studies employing α-conotoxins have identified a novel target, the α9α10 subtype, with potential importance for pain management. Antagonism of the α9α10 nAChR by peptide α-conotoxins produced analgesia in rodent models of neuropathic and inflammatory pain. In order to evaluate non-peptide antagonists of this subtype, we have recently synthesized a series of tetrakis-, tris-, and bis-quaternary ammonium salts. Compounds from each group, GZ-5-56A, ZZ-2-04G and ZZ-1-61C, respectively, were found to block rat α9α10 nAChRs expressed in Xenopus oocytes with IC50s in a range similar to those for the analgesic α-conotoxins previously tested. These analogs had selectivity for α9α10 nAChR when compared to other nAChRs (e.g., α7). Parenteral administration of GZ-5-56A and ZZ-2-04G in a dose-related manner reversed mechanical hyperalgesia in a rodent (Sprague-Dawley male rats) model of neuropathic pain (chronic constriction nerve injury, CCI) and alleviated persistent inflammatory pain in the formalin test. Analgesia was not confounded by motor impairment (rotarod). Tolerance was not observed with repeated dosing (CCI). Neither compound was effective in the tail-flick model of acute nociception. Testing with ZZ-1-61C demonstrated analgesic activity in the formalin test following both parenteral and oral administration. These preclinical data suggest that novel quaternary ammonium salts may be potential candidates for development as analgesics with a unique mechanism of action at the α9α10 receptor. (Support: NIH U19 DA017548, RO1 MH5363, DA022091.)" @default.
- W2045131433 created "2016-06-24" @default.
- W2045131433 creator A5000855403 @default.
- W2045131433 creator A5007020543 @default.
- W2045131433 creator A5030875271 @default.
- W2045131433 creator A5049488705 @default.
- W2045131433 creator A5083049265 @default.
- W2045131433 date "2010-04-01" @default.
- W2045131433 modified "2023-09-23" @default.
- W2045131433 title "Novel small molecule alpha9 alpha10 nicotinic receptor antagonists for pain management" @default.
- W2045131433 doi "https://doi.org/10.1016/j.jpain.2010.01.138" @default.
- W2045131433 hasPublicationYear "2010" @default.
- W2045131433 type Work @default.
- W2045131433 sameAs 2045131433 @default.
- W2045131433 citedByCount "3" @default.
- W2045131433 countsByYear W20451314332012 @default.
- W2045131433 crossrefType "journal-article" @default.
- W2045131433 hasAuthorship W2045131433A5000855403 @default.
- W2045131433 hasAuthorship W2045131433A5007020543 @default.
- W2045131433 hasAuthorship W2045131433A5030875271 @default.
- W2045131433 hasAuthorship W2045131433A5049488705 @default.
- W2045131433 hasAuthorship W2045131433A5083049265 @default.
- W2045131433 hasBestOaLocation W20451314331 @default.
- W2045131433 hasConcept C118552586 @default.
- W2045131433 hasConcept C126322002 @default.
- W2045131433 hasConcept C15490471 @default.
- W2045131433 hasConcept C170493617 @default.
- W2045131433 hasConcept C175234850 @default.
- W2045131433 hasConcept C185592680 @default.
- W2045131433 hasConcept C188987157 @default.
- W2045131433 hasConcept C2777107010 @default.
- W2045131433 hasConcept C2779245659 @default.
- W2045131433 hasConcept C2779281246 @default.
- W2045131433 hasConcept C2780820201 @default.
- W2045131433 hasConcept C2781118164 @default.
- W2045131433 hasConcept C42219234 @default.
- W2045131433 hasConcept C55493867 @default.
- W2045131433 hasConcept C71924100 @default.
- W2045131433 hasConcept C80161118 @default.
- W2045131433 hasConcept C98274493 @default.
- W2045131433 hasConceptScore W2045131433C118552586 @default.
- W2045131433 hasConceptScore W2045131433C126322002 @default.
- W2045131433 hasConceptScore W2045131433C15490471 @default.
- W2045131433 hasConceptScore W2045131433C170493617 @default.
- W2045131433 hasConceptScore W2045131433C175234850 @default.
- W2045131433 hasConceptScore W2045131433C185592680 @default.
- W2045131433 hasConceptScore W2045131433C188987157 @default.
- W2045131433 hasConceptScore W2045131433C2777107010 @default.
- W2045131433 hasConceptScore W2045131433C2779245659 @default.
- W2045131433 hasConceptScore W2045131433C2779281246 @default.
- W2045131433 hasConceptScore W2045131433C2780820201 @default.
- W2045131433 hasConceptScore W2045131433C2781118164 @default.
- W2045131433 hasConceptScore W2045131433C42219234 @default.
- W2045131433 hasConceptScore W2045131433C55493867 @default.
- W2045131433 hasConceptScore W2045131433C71924100 @default.
- W2045131433 hasConceptScore W2045131433C80161118 @default.
- W2045131433 hasConceptScore W2045131433C98274493 @default.
- W2045131433 hasIssue "4" @default.
- W2045131433 hasLocation W20451314331 @default.
- W2045131433 hasOpenAccess W2045131433 @default.
- W2045131433 hasPrimaryLocation W20451314331 @default.
- W2045131433 hasRelatedWork W1969936443 @default.
- W2045131433 hasRelatedWork W1981410744 @default.
- W2045131433 hasRelatedWork W1999864181 @default.
- W2045131433 hasRelatedWork W2032713313 @default.
- W2045131433 hasRelatedWork W2062232248 @default.
- W2045131433 hasRelatedWork W2141733322 @default.
- W2045131433 hasRelatedWork W2145565627 @default.
- W2045131433 hasRelatedWork W2147909455 @default.
- W2045131433 hasRelatedWork W2414357090 @default.
- W2045131433 hasRelatedWork W2167446171 @default.
- W2045131433 hasVolume "11" @default.
- W2045131433 isParatext "false" @default.
- W2045131433 isRetracted "false" @default.
- W2045131433 magId "2045131433" @default.
- W2045131433 workType "article" @default.