The analgesic effect profile of FR122047, a selective cyclooxygenase-1 inhibitor, in chemical nociceptive models

Ochi, Takehiro; Motoyama, Yukio; Goto, Toshio

doi:10.1016/s0014-2999(00)00051-0

Cited by 82 publications

(61 citation statements)

References 22 publications

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“…increases levels of PGE2 and PGF2α in peritoneal fluids as well as lipoxygenase products (Ochi et al, 2000). It was found that extract significantly inhibited the acetic acid induced writhing response.…”

Section: Resultsmentioning

confidence: 95%

“…In this test the animals react with characteristic stretching behavior, which is called writhing. Acetic acid causes algesia by liberating endogenous substances including serotonin, histamine, PGs, bradykinin and substance P which stimulate pain nerve endings (Ochi et al, 2000). Local peritoneal receptors are postulated to be partly involved in the abdominal constriction (writhing) response.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Analgesic and anti-inflammatory activities of leaf extract of Kydia calycina Roxb.

Bhukya

Anreddy

William

et al. 2009

Bangladesh J Pharmacol

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Analgesic and anti-inflammatory activities of leaf extract of Kydia calycina Roxb.

Bhukya

Anreddy

William

et al. 2009

Bangladesh J Pharmacol

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“…COX-2-selective drugs, for example, are clinically useful in inhibiting inflammatory pain in humans (13) and are more potent than COX-1-selective NSAIDs at inhibiting pain induced by proinflammatory agents (e.g., carrageenan) in some paw inflammation assays in rodents (14,15). COX-1-selective drugs, in contrast, are superior to COX-2-selective agents at inhibiting visceronociception caused by a variety of chemical pain stimulators (16)(17)(18). Moreover, Ballou and colleagues (19) found that visceronociception was greatly decreased in COX-1 but not COX-2 knockout mice.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Ballou and colleagues (19) found that visceronociception was greatly decreased in COX-1 but not COX-2 knockout mice. Both COX-1 and -2, on the other hand, have been implicated in nociception models that measure analgesia outside the gut, such as in formalin and urate crystal tests (18)(19)(20). A role for COX-1 in pain is further supported by the fact that COX-1-selective NSAIDs [e.g., as identified by Warner and colleagues (21)]-such as aspirin, ketorolac, ketoprofen, ibuprofen, and suprofen-are clinically important analgesic agents in humans and animals.…”

Section: Discussionmentioning

confidence: 99%

COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression

Chandrasekharan

Dai

Roos

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

1,679

1,111

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Two cyclooxygenase isozymes, COX-1 and -2, are known to catalyze the rate-limiting step of prostaglandin synthesis and are the targets of nonsteroidal antiinflammatory drugs. Here we describe a third distinct COX isozyme, COX-3, as well as two smaller COX-1-derived proteins (partial COX-1 or PCOX-1 proteins). COX-3 and one of the PCOX-1 proteins (PCOX-1a) are made from the COX-1 gene but retain intron 1 in their mRNAs. PCOX-1 proteins additionally contain an in-frame deletion of exons 5-8 of the COX-1 mRNA. COX-3 and PCOX mRNAs are expressed in canine cerebral cortex and in lesser amounts in other tissues analyzed. In human, COX-3 mRNA is expressed as an Ϸ5.2-kb transcript and is most abundant in cerebral cortex and heart. Intron 1 is conserved in length and in sequence in mammalian COX-1 genes. This intron contains an ORF that introduces an insertion of 30 -34 aa, depending on the mammalian species, into the hydrophobic signal peptide that directs COX-1 into the lumen of the endoplasmic reticulum and nuclear envelope. COX-3 and PCOX-1a are expressed efficiently in insect cells as membrane-bound proteins. The signal peptide is not cleaved from either protein and both proteins are glycosylated. COX-3, but not PCOX-1a, possesses glycosylation-dependent cyclooxygenase activity. Comparison of canine COX-3 activity with murine COX-1 and -2 demonstrates that this enzyme is selectively inhibited by analgesic/antipyretic drugs such as acetaminophen, phenacetin, antipyrine, and dipyrone, and is potently inhibited by some nonsteroidal antiinflammatory drugs. Thus, inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.A cetaminophen is often categorized as a nonsteroidal antiinflammatory drug (NSAID), even though in clinical practice and in animal models it possesses little antiinflammatory activity (1). Like NSAIDs, however, acetaminophen inhibits pain and fever and is one of the world's most popular analgesic/ antipyretic drugs. Despite acetaminophen's long use and popularity it lacks a clear mechanism of action. Flower and Vane showed that acetaminophen inhibited cyclooxygenase (COX) activity in dog brain homogenates more than in homogenates from spleen (2). This gave rise to the concept that variants of COX enzymes exist that are differentially sensitive to this drug and that acetaminophen acts centrally. Yet, even though two isozymes of COX are known, neither isozyme is sensitive to acetaminophen at therapeutic concentrations of the drug in whole cells or homogenates. Instead, COX-1 and -2 in homogenates frequently exhibit the paradoxical property of being stimulated by submillimolar concentrations of acetaminophen and inhibited by supermillimolar levels of the drug (1). This finding suggests that neither isozyme is a good candidate for the site of action of acetaminophen.In analyzing COX-1 and -2 RNA expression in dog tissues, our laboratory observed that the cerebral cortex of dog brain contains two distinct RNAs that hybridized to a canine COX-1 cDNA. ...

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“…FR122047, a selective COX-1 inhibitor was reported to have an analgesic effect in chemical nociceptive models and an anti-inflammatory effect in animal models of chronic inflammtion (17,18) but the anti-cancer activity of the chemical has not yet been identified. Here, we report that exposure of MCF-7 breast cancer cells to FR122047, a COX-1 inhibitor resulted in a dose-dependent cell growth arrest and apoptotic cell death.…”

Section: Introductionmentioning

confidence: 99%

Induction of cell growth arrest and apoptotic cell death in human breast cancer MCF-7 cells by the COX-1 inhibitor FR122047

Jeong

Kim²,

Choi³

et al. 2010

Oncol Rep

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Abstract. Non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit the enzyme cyclooxygenase (COX), are known to have a potent anti-tumorigenic activity in various cancers. However, the responsible molecular mechanisms of COX inhibition in breast cancer cells remain to be completely elucidated. We examined the effect of the selective COX-1 inhibitor, FR122047 and the selective COX-2 inhibitor, SC791 on cell growth and apoptosis in human breast cancer MCF-7 cells which exhibited a high basal level of COX-1 expression. Compared to SC791, FR122047 treatment led to a distinct suppression of cell growth in MCF-7 cells. Upon FR122047 treatment, there were apparent increases in the ratio of Bax to Bcl-2, mitochondrial cytochrome c release, and apoptosis in MCF-7 cells. Our data showed that treatment of caspase-8 inhibitor could significantly suppress the cleavage of the effector caspase-7 and PARP in FR122047-treated MCF-7 cells which are caspase-3-deficient breast cancer cells, indicating that the induction of apoptosis by FR122047 is significantly dependent on caspase-8 activity in MCF-7 breast cancer cells. Our data suggest that the NSAID FR122047 may have an anti-cancer potential in breast cancer.

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The analgesic effect profile of FR122047, a selective cyclooxygenase-1 inhibitor, in chemical nociceptive models

Cited by 82 publications

References 22 publications

Analgesic and anti-inflammatory activities of leaf extract of Kydia calycina Roxb.

Analgesic and anti-inflammatory activities of leaf extract of Kydia calycina Roxb.

COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression

Induction of cell growth arrest and apoptotic cell death in human breast cancer MCF-7 cells by the COX-1 inhibitor FR122047

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