Topic
Phenidone
About: Phenidone is a research topic. Over the lifetime, 258 publications have been published within this topic receiving 6589 citations. The topic is also known as: phenidone.
Papers published on a yearly basis
Papers
TL;DR: Not surprisingly, drugs were more effective models were somewhat selective for CO and CO/LO inhibitors; however, dapsone was orally effective in the ear models, and a number of mediator antagonists and CNS drugs, especially anti-psychotics, were topically active primarily against TPA edema.
Abstract: Inhibitors of arachidonic acid (AA) metabolism and other pharmacologic agents were evaluated against ear edema produced in mice by tetradecanoylphorbol acetate (TPA) or AA. Drugs were administered orally and topically either 30 min prior to AA or 30 min after TPA, except for steroids which were administered 2.5-3 hr prior to AA. Several cyclooxygenase (CO) inhibitors including indomethacin, aspirin, piroxicam and timegadine were without effect when administered orally against either irritant; the same drugs inhibited TPA edema when they were administered topically. Mixed CO/lipoxygenase (LO) inhibitors, phenidone and BW755C, were active orally against AA edema (ED50S of 84 and 65 mg/kg, respectively) and against TPA edema (ED50S of 235 and 88 mg/kg, respectively). Phenidone was more active topically against AA edema (ED50, 0.1 mg/ear) than BW755C (ED50, 2.8 mg/ear); however, BW755C was more active topically against TPA edema (ED50, 0.2 mg/ear) than phenidone (ED50, 0.6 mg/ear). Methylprednisolone was very effective in the AA (oral ED50, 17 mg/kg; topical ED50, greater than 1 mg/ear) and TPA models (oral ED50, 4.3 mg/kg; topical ED50, 0.03 mg/ear. MK-447 was topically and orally effective only in the TPA model. Not surprisingly, drugs were more effective topically than orally in both mouse ear edema assays. The models were somewhat selective for CO and CO/LO inhibitors; however, dapsone was orally effective in the ear models, and a number of mediator antagonists and CNS drugs, especially anti-psychotics, were topically active primarily against TPA edema. These models may be useful for the detection of in vivo activity of CO/LO or 5-LO inhibitors.
331 citations
TL;DR: The bio‐transformation of the free arachidonic acid, by the enzyme cyclo‐oxygenase, to the unstable endoperoxide intermediates is inhibited by non‐steroidal anti‐inflammatory agents, and the generation of all the prostaglandin products is prevented.
Abstract: Drugs may alter prostaglandin production by acting on the various pathways of arachidonic acid metabolism. The liberation of arachidonic acid from membrane-bound phospholipids, induced by the enzyme phospholipase A2, may be inhibited by mepacrine and the steroidal anti-inflammatory agents. The bio-transformation of the free arachidonic acid, by the enzyme cyclooxygenase, to the unstable endoperoxide intermediates is inhibited by non-steroidal anti-inflammatory agents. Thus, the generation of all the prostaglandin products is prevented. This action can explain the anti-inflammatory, analgesic, antipyretic actions as well as the ulcerogenic properties of these aspirin-like compounds. An alternative metabolic pathway of arachidonic acid, via the lipoxygenase system, can be inhibited by an acetylenic analogue and a newer compound, phenidone. The unstable endoperoxide intermediates can be transformed by blood platelets into the pro-aggregating products, thromboxanes. This pathway can be selectively inhibited by a variety of experimental compounds. Prostacyclin, a potent vasodilator and inhibitor of platelet aggregation is the major product of endoperoxide transformation in blood vessels. Its formation can be inhibited by lipid peroxides. Selective actions on one or more steps in arachidonic acid metabolism can lead to a different profile of the products subsequently generated. Such a diversion of biosynthetic pathways may be an underlying mechanism in certain pathological conditions, perhaps even in dysmenorrhea.
240 citations
TL;DR: The mechanism of the inhibitory action of phenidone, 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline, dithiothreitol, hydroquinone, and pyrogallol on the vascular relaxation induced by endothelium-derived relaxing factor was investigated and indicates that the above five inhibitors inactivate EDRF through the formation of superoxide ions.
Abstract: The mechanism of the inhibitory action of phenidone, 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C), dithiothreitol, hydroquinone, and pyrogallol on the vascular relaxation induced by endothelium-derived relaxing factor (EDRF) was investigated. EDRF was released from porcine aortic endothelial cells in culture and bioassayed on a cascade of superfused rabbit aortic strips. These compounds inhibited EDRF-induced relaxation of vascular strips, without affecting the relaxation induced by glyceryl trinitrate, and their inhibitory potency was markedly attenuated (by more than 1 order of magnitude) by the addition of superoxide dismutase (5-15 units/ml) or oxidized cytochrome c (20-40 microM) but not by catalase (30 units/ml) or heat-inactivated superoxide dismutase. These data indicate that the above five inhibitors inactivate EDRF through the formation of superoxide ions, which have recently been shown to destroy EDRF. The inhibition of EDRF by these compounds is therefore attributable to their redox properties rather than to any specific biological action.
229 citations
TL;DR: 1-phenyl-3-pyrazolidone (phenidone) is a commercially available reagent used in the photographic industry and when tested as an inhibitor of arachidonic acid metabolsim in platelets and lungs it was found to be effective against both the cyclo-oxygenase and lipoxygenases pathways.
139 citations
TL;DR: It is demonstrated that ketoconazole is a comparatively specific and orally active inhibitor of the 5-lipoxygenase activity bearing on the production of leukotrienes derived from arachidonic acid.
136 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2018 | 2 |
| 2014 | 3 |
| 2013 | 1 |
| 2011 | 3 |
| 2010 | 2 |
| 2009 | 2 |