The Experts below are selected from a list of 111 Experts worldwide ranked by ideXlab platform
Brigitta M. Peskar - One of the best experts on this subject based on the ideXlab platform.
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aspirin like drugs may block pain independently of Prostaglandin Synthesis Inhibition
Cellular and Molecular Life Sciences, 1991Co-Authors: Kay Brune, W S Beck, S Menzelsoglowek, Gerd Geisslinger, Brigitta M. PeskarAbstract:Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that Prostaglandin Synthesis Inhibition is primarily mediating the anti-inflammatory activity but Prostaglandin Synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited Prostaglandin Synthesis, inflammation and nociception in rats. The R-form had much less effect on Prostaglandin Synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.
Keith Mccormack - One of the best experts on this subject based on the ideXlab platform.
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Non-steroidal anti-inflammatory drugs and spinal nociceptive processing.
Pain, 1994Co-Authors: Keith MccormackAbstract:Non-steroidal anti-inflammatory drugs have a direct action on spinal nociceptive processing in vivo with a relative order of potency which correlates with their capacity as inhibitors of cyclooxygenase activity. However, recent clinical surveys and new in vivo evidence strongly suggest that for some of these agents, centrally mediated analgesia may also be achieved by additional mechanisms, which are independent of Prostaglandin Synthesis Inhibition. In this review we explore the likelihood for such mechanisms following an extensive survey of existing data. The implications of these mechanisms are discussed in the light of our current understanding of spinal nociceptive processing.
Kay Brune - One of the best experts on this subject based on the ideXlab platform.
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Antinociceptive actions of R(-)-flurbiprofen--a non-cyclooxygenase inhibiting 2-arylpropionic acid--in rats.
Life sciences, 1994Co-Authors: Gerd Geisslinger, Sérgio H. Ferreira, S. Menzel, Detlef Schlott, Kay BruneAbstract:Intraperitoneal administration of R(−)- amd S(+)-flurbiprofen resulted in dose dependent antinociceptive behavior in the rat paw formalin test. S(+)-flurbiprofen was significantly more potent than the non-cyclooxygenase inhibiting R(−)-enantiomer with a potency ratio of about 3 to 1. Chiral inversion was very low and does not seem to account for the action of R(−)-flurbiprofen. In a modified Randall Selitto assay also both enantiomers were active in a dose dependent manner following systemic administration. Following local administration into the inflamed paw only S(+)-flurbiprofen showed significant dose related antinociceptive effects. R(−)-flurbiprofen was unable to block Prostaglandin E2 induced hyperalgesia following local administration. Consequently, a central site of action independent of Prostaglandin Synthesis Inhibition has to be discussed with respect to antinociceptive activity following systemic administration.
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aspirin like drugs may block pain independently of Prostaglandin Synthesis Inhibition
Cellular and Molecular Life Sciences, 1991Co-Authors: Kay Brune, W S Beck, S Menzelsoglowek, Gerd Geisslinger, Brigitta M. PeskarAbstract:Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that Prostaglandin Synthesis Inhibition is primarily mediating the anti-inflammatory activity but Prostaglandin Synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited Prostaglandin Synthesis, inflammation and nociception in rats. The R-form had much less effect on Prostaglandin Synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.
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Analgesia by Nonopiate Analgesics May Not Necessarily Depend on Prostaglandin Synthesis Inhibition
Drug Investigation, 1991Co-Authors: Kay Brune, W S BeckAbstract:Nonopioid analgesics are believed to exert their anti-inflammatory and analgesic activities via Inhibition of the cyclo-oxygenase system particularly in inflamed tissue. However, there is no satisfying correlation between Prostaglandin (PG) Synthesis Inhibition and analgesic effects. Investigating flurbiprofen, a chiral 2-arylpropionic acid derivative, were obtained evidence that PG Synthesis Inhibition is mediating the anti-inflammatory activity ( S -enantiomer), but that PG Synthesis independent mechanisms contribute to the analgesic effects ( R -enantiomer). Nevertheless, it cannot be excluded that a reduction of the PG Synthesis within the CNS by nonopioid analgesics mediates the analgesic effect observed.
Gerd Geisslinger - One of the best experts on this subject based on the ideXlab platform.
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Cyclooxygenase-independent actions of cyclooxygenase inhibitors
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2000Co-Authors: Irmgard Tegeder, Josef Pfeilschifter, Gerd GeisslingerAbstract:Several studies have demonstrated unequivocally that certain nonsteroidal anti-inflammatory drugs (NSAIDs) such as sodium salicylate, sulindac, ibuprofen, and flurbiprofen cause anti-inflammatory and antiproliferative effects independent of cyclooxygenase activity and Prostaglandin Synthesis Inhibition. These effects are mediated through Inhibition of certain transcription factors such as NF-κB and AP-1. The respective NSAIDs might interfere directly with the transcription factors, but their effects are probably mediated predominantly through alterations of the activity of cellular kinases such as IKKβ, Erk, p38 MAPK, or Cdks. These effects apparently are not shared by all NSAIDs, since indomethacin failed to inhibit NF-κB and AP-1 activation as well as Erk and Cdk activity. In contrast, indomethacin was able to activate PPARγ, which was not affected by sodium salicylate or aspirin. The differences in cyclooxygenase-independent mechanisms may have consequences for the specific use of these drugs in indivi...
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Antinociceptive actions of R(-)-flurbiprofen--a non-cyclooxygenase inhibiting 2-arylpropionic acid--in rats.
Life sciences, 1994Co-Authors: Gerd Geisslinger, Sérgio H. Ferreira, S. Menzel, Detlef Schlott, Kay BruneAbstract:Intraperitoneal administration of R(−)- amd S(+)-flurbiprofen resulted in dose dependent antinociceptive behavior in the rat paw formalin test. S(+)-flurbiprofen was significantly more potent than the non-cyclooxygenase inhibiting R(−)-enantiomer with a potency ratio of about 3 to 1. Chiral inversion was very low and does not seem to account for the action of R(−)-flurbiprofen. In a modified Randall Selitto assay also both enantiomers were active in a dose dependent manner following systemic administration. Following local administration into the inflamed paw only S(+)-flurbiprofen showed significant dose related antinociceptive effects. R(−)-flurbiprofen was unable to block Prostaglandin E2 induced hyperalgesia following local administration. Consequently, a central site of action independent of Prostaglandin Synthesis Inhibition has to be discussed with respect to antinociceptive activity following systemic administration.
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aspirin like drugs may block pain independently of Prostaglandin Synthesis Inhibition
Cellular and Molecular Life Sciences, 1991Co-Authors: Kay Brune, W S Beck, S Menzelsoglowek, Gerd Geisslinger, Brigitta M. PeskarAbstract:Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that Prostaglandin Synthesis Inhibition is primarily mediating the anti-inflammatory activity but Prostaglandin Synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited Prostaglandin Synthesis, inflammation and nociception in rats. The R-form had much less effect on Prostaglandin Synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.
Keith A - One of the best experts on this subject based on the ideXlab platform.
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Prostaglandin Synthesis Inhibition restores hypoxic pulmonary vasoconstriction
2016Co-Authors: J.m. Alexander, M. D. Nyby, A. Jasberg, John M, Keith AAbstract:nary vasoconstriction in blood-perfused isolated dog lungs pro-gressively diminishes with repeated hypoxic challenges. We investigated the role of Prostaglandins in effecting the decay of the hypoxic response by using a double perfusion preparation that could separately perfuse the right and left lungs of a single dog. Degeneration of this response was reversed by the addition of Prostaglandin (PG) Synthesis inhibitors, aspirin, or indomethacin. Various PG’s known to be produced by the lung (PGE,, PGE.,, and PGF,,,), were infused, and only PGE, abol-ished hypoxic pulmonary vasoconstriction. Since other work-ers have shown that lungs can synthesize and release PG’s in response to various stimuli, we postulate that PGE, Synthesis in isolated lungs may increase and thereby cause the degener-ation of the hypoxic response. The addition of aspirin or indo-methacin could inhibit the Synthesis of PGE, and thereb
