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Journal ArticleDOI

Anti-inflammatory drugs and their mechanism of action

John R. Vane, +1 more
- 01 Oct 1998 - 
- Vol. 47, Iss: 2, pp 78-87
TLDR
Selective COX-2 inhibitors may demonstrate new important therapeutic benefits as anticancer agents, as well as in preventing premature labor and perhaps even retarding the progression of Alzheimer's disease.
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their therapeutic activities through inhibition of cyclooxygenase (COX), the enzyme that makes prostaglandins (PGs). They share, to a greater or lesser degree, the same side effects, including gastric and renal toxicity. Recent research has shown that there are at least two COX isoenzymes. COX-1 is constitutive and makes PGs that protect the stomach and kidney from damage. COX-2 is induced by inflammatory stimuli, such as cytokines, and produces PGs that contribute to the pain and swelling of inflammation. Thus, selective COX-2 inhibitors should be anti-inflammatory without side effects on the kidney and stomach. Of course, selective COX-2 inhibitors may have other side effects and perhaps other therapeutic potential. For instance, COX-2 (and not COX-1) is thought to be involved in ovulation and in labor. In addition, the well-known protective action of aspirin on colon cancer may be through an action on COX-2, which is expressed in this disease. Moreover, NSAIDs delay the progress of Alzheimer's disease. Thus, selective COX-2 inhibitors may demonstrate new important therapeutic benefits as anticancer agents, as well as in preventing premature labor and perhaps even retarding the progression of Alzheimer's disease.

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Citations
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Journal ArticleDOI

Risk of cardiovascular events associated with selective COX-2 inhibitors.

TL;DR: The results from VIGOR showed that the relative risk of developing a confirmed adjudicated thrombotic cardiovascular event with rofecoxib treatment compared with naproxen was higher than that in the placebo group of a recent meta-analysis of 23 407 patients in primary prevention trials.
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Chronic inflammation and cancer.

TL;DR: The contribution of reactive oxygen and nitrogen intermediates, prostaglandins, and inflammatory cytokines to carcinogenesis is discussed, which can lead to novel approaches to the prevention and treatment of cancer.
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Nonsteroidal Anti-inflammatory Drugs and the Risk of Parkinson Disease

TL;DR: Findings are consistent with the hypothesis that use of NSAIDs may delay or prevent the onset of PD.
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Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of β-Amyloid-Stimulated Proinflammatory Responses and Neurotoxicity by PPARγ Agonists

TL;DR: The efficacy of NSAIDs in the treatment of AD may be a consequence of their actions on PPARγ rather than on their canonical targets the cyclooxygenases, and the efficacy of these agents in inhibiting a broad range of inflammatory responses suggestsPPARγ agonists may provide a novel therapeutic approach to AD.
References
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Journal ArticleDOI

Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs

TL;DR: Experiments with guinea-pig lung suggest that some of the therapeutic effects of sodium salicylate and aspirin-like drugs are due to inhibition of the synthesis of prostaglandins.
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An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation.

TL;DR: A balance between formation of anti- and pro-aggregatory substances by enzymes could also contribute to the maintenance of the integrity of vascular endothelium and explain the mechanism of formation of intra-arterial thrombi in certain physiopathological conditions.
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Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides.

TL;DR: Evidence is presented that the more unstable and major component of rabbit aorta contracting substance (RCS) formed in platelets and guinea pig lung is also thromboxane A2.
Journal ArticleDOI

Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas

TL;DR: COX-2, but not COX-1, gene expression is markedly elevated in most human colorectal cancers compared with accompanying normal mucosa, and COx-2 expression seems to be increased in a subset of adenomas.
Journal ArticleDOI

Suppression of Intestinal Polyposis in ApcΔ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2)

TL;DR: Results provide direct genetic evidence that COX-2 plays a key role in tumorigenesis and indicate that COx-2-selective inhibitors can be a novel class of therapeutic agents for colorectal polyposis and cancer.
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