Matches in SemOpenAlex for { <https://semopenalex.org/work/W2080294583> ?p ?o ?g. }
- W2080294583 endingPage "470" @default.
- W2080294583 startingPage "463" @default.
- W2080294583 abstract "SK&F 95654 inhibited the guanosine 3′:5′‐cyclic monophosphate (cyclic GMP)‐inhibited phosphodiesterase (cGI‐PDE) with an IC 50 value of 0.7 μ m . The IC 50 values were greater than 100 μ m for the other four phosphodiesterase isoenzymes tested. The R ‐enantiomer of SK&F 95654 (IC 50 = 0.35 μ m ) was a more potent inhibitor of cGI‐PDE than was the S ‐enantiomer (IC 50 = 5.3 μ m ). In the guinea‐pig working heart, SK&F 95654 produced a positive inotropic response without altering heart rate. Oral administration of SK&F 95654 to conscious dogs caused dose‐dependent increases in left ventricular dp / dt max in the range 10–50 μg kg −1 . These positive inotropic responses were maintained for 3 h without simultaneous changes in heart rate or blood pressure. The peak effects on left ventricular dp / dt max were similar for orally and intravenously administered compound, indicating good oral bioavailability. SK&F 95654 caused a potent inhibition of U46619‐induced aggregation in both a human washed platelet suspension (WPS) (IC 50 = 70 n m ) and in human platelet‐rich plasma (PRP) (IC 50 = 60 n m ), indicating that the compound shows negligible plasma binding. The R ‐enantiomer of SK&F 95654 was twenty fold more potent as an inhibitor of platelet aggregation than was the S ‐enantiomer. The similarity of this ratio to that obtained on the cGI‐PDE suggests that SK&F 95654 inhibits platelet aggregation via its effects on cGI‐PDE. This was also indicated by studies which showed that SK&F 95654 increased adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) levels and activated cyclic AMP‐dependent protein kinase in human platelets. 6 Collagen‐induced aggregation of rat PRP was also inhibited by SK&F 95654 (IC 50 = 65 n m ). The effects of SK&F 95654, administered intravenously, on ex vivo platelet aggregation were studied in the conscious rat. At 1 mg kg −1 , SK&F 95654 inhibited aggregation for at least 4 h post dose and was more potent than the two other cGI‐PDE inhibitors studied (siguazodan and SK&F 94120). 7 In contrast to its potent effects on heart and platelets, SK&F 95654 caused only a modest relaxation of histamine‐ or U46619‐induced bronchoconstriction in the anaesthetized, ventilated guinea‐pig. 8 Taken together, these results indicate that SK&F 95654 may be a suitable agent for the treatment of congestive heart failure." @default.
- W2080294583 created "2016-06-24" @default.
- W2080294583 creator A5004710358 @default.
- W2080294583 creator A5006149515 @default.
- W2080294583 creator A5023019824 @default.
- W2080294583 creator A5029723682 @default.
- W2080294583 creator A5038906086 @default.
- W2080294583 creator A5054492220 @default.
- W2080294583 creator A5064800623 @default.
- W2080294583 creator A5069907096 @default.
- W2080294583 creator A5072789325 @default.
- W2080294583 creator A5088815397 @default.
- W2080294583 date "1992-10-01" @default.
- W2080294583 modified "2023-10-17" @default.
- W2080294583 title "The effect of SK&F 95654, a novel phosphodiesterase inhibitor, on cardiovascular, respiratory and platelet function" @default.
- W2080294583 cites W1593151186 @default.
- W2080294583 cites W187129005 @default.
- W2080294583 cites W1936333617 @default.
- W2080294583 cites W1970569585 @default.
- W2080294583 cites W1973130007 @default.
- W2080294583 cites W1977459466 @default.
- W2080294583 cites W1982677020 @default.
- W2080294583 cites W1986730217 @default.
- W2080294583 cites W1996967254 @default.
- W2080294583 cites W2006446901 @default.
- W2080294583 cites W2015670412 @default.
- W2080294583 cites W2017080249 @default.
- W2080294583 cites W2019430022 @default.
- W2080294583 cites W2019919832 @default.
- W2080294583 cites W2027298594 @default.
- W2080294583 cites W2027776339 @default.
- W2080294583 cites W2046780540 @default.
- W2080294583 cites W2062601916 @default.
- W2080294583 cites W2068494902 @default.
- W2080294583 cites W2071331983 @default.
- W2080294583 cites W2071437372 @default.
- W2080294583 cites W2074684694 @default.
- W2080294583 cites W2080955714 @default.
- W2080294583 cites W2100485151 @default.
- W2080294583 cites W2101228796 @default.
- W2080294583 cites W2106012387 @default.
- W2080294583 cites W2112852642 @default.
- W2080294583 cites W2137368124 @default.
- W2080294583 cites W2226662642 @default.
- W2080294583 cites W2264789091 @default.
- W2080294583 cites W2302932420 @default.
- W2080294583 cites W2319534362 @default.
- W2080294583 cites W2343098797 @default.
- W2080294583 cites W2399427399 @default.
- W2080294583 cites W2258075813 @default.
- W2080294583 doi "https://doi.org/10.1111/j.1476-5381.1992.tb12768.x" @default.
- W2080294583 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1907861" @default.
- W2080294583 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1422592" @default.
- W2080294583 hasPublicationYear "1992" @default.
- W2080294583 type Work @default.
- W2080294583 sameAs 2080294583 @default.
- W2080294583 citedByCount "21" @default.
- W2080294583 countsByYear W20802945832016 @default.
- W2080294583 countsByYear W20802945832017 @default.
- W2080294583 countsByYear W20802945832019 @default.
- W2080294583 countsByYear W20802945832021 @default.
- W2080294583 countsByYear W20802945832022 @default.
- W2080294583 crossrefType "journal-article" @default.
- W2080294583 hasAuthorship W2080294583A5004710358 @default.
- W2080294583 hasAuthorship W2080294583A5006149515 @default.
- W2080294583 hasAuthorship W2080294583A5023019824 @default.
- W2080294583 hasAuthorship W2080294583A5029723682 @default.
- W2080294583 hasAuthorship W2080294583A5038906086 @default.
- W2080294583 hasAuthorship W2080294583A5054492220 @default.
- W2080294583 hasAuthorship W2080294583A5064800623 @default.
- W2080294583 hasAuthorship W2080294583A5069907096 @default.
- W2080294583 hasAuthorship W2080294583A5072789325 @default.
- W2080294583 hasAuthorship W2080294583A5088815397 @default.
- W2080294583 hasBestOaLocation W20802945831 @default.
- W2080294583 hasConcept C126322002 @default.
- W2080294583 hasConcept C134018914 @default.
- W2080294583 hasConcept C155710745 @default.
- W2080294583 hasConcept C181199279 @default.
- W2080294583 hasConcept C185592680 @default.
- W2080294583 hasConcept C2776766087 @default.
- W2080294583 hasConcept C2777995097 @default.
- W2080294583 hasConcept C2780994212 @default.
- W2080294583 hasConcept C486523 @default.
- W2080294583 hasConcept C519581460 @default.
- W2080294583 hasConcept C55493867 @default.
- W2080294583 hasConcept C62826618 @default.
- W2080294583 hasConcept C71240020 @default.
- W2080294583 hasConcept C71924100 @default.
- W2080294583 hasConcept C89560881 @default.
- W2080294583 hasConcept C98274493 @default.
- W2080294583 hasConceptScore W2080294583C126322002 @default.
- W2080294583 hasConceptScore W2080294583C134018914 @default.
- W2080294583 hasConceptScore W2080294583C155710745 @default.
- W2080294583 hasConceptScore W2080294583C181199279 @default.
- W2080294583 hasConceptScore W2080294583C185592680 @default.
- W2080294583 hasConceptScore W2080294583C2776766087 @default.
- W2080294583 hasConceptScore W2080294583C2777995097 @default.
- W2080294583 hasConceptScore W2080294583C2780994212 @default.