L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-4-benzofuranol): a novel, selective, orally active 5-lipoxygenase inhibitor

Bélanger, P. C.; Maycock, Alan L.; Guindon, Yvan; Bach, Thomas J.; Dollob, A. L.; Dufresne, Claude; Ford‐Hutchinson, A. W.; Gale, Paul H.; Hopple, S.; Lau, Cheuk K.; Letts, L. Gordon; Luell, Silvi; Mcfarlane, C. S.; MacIntyre, Euan; Meurer, Roger; Miller, Douglas K.; Piechuta, H.; Riendeau, Denis; Rokach, Joshua; Rouzer, Carol A.; Scheigetz, John

doi:10.1139/y87-387

Cited by 31 publications

(9 citation statements)

References 23 publications

(21 reference statements)

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“…5 Se ve ral stu di es suggest that PAF might exag ge ra te pa in. 6,7 PAF is produ ced by va ri o us kinds of cells inc lu ding ke ra tinocy tes 8 and inf lam ma tory cells, 9 and the le vel of PAF is in cre a sed in inf la med tis su e, 10 In addition, du ring hypo xi a, isc he mi a and in ot her pat ho lo gic con di ti ons in vol ving oxi da ti ve stress, PAF con centra ti on in cre a ses and it be co mes a pro-inf lam matory mes sen ger and a me di a tor of ne u ro to xi city.…”

mentioning

confidence: 99%

Protective Effects of Platelet-Activating Factor Antagonist ABT-491 on the Peripheral Nerves in Hypoxic Ischemia-Induced Neonatal Rat Model

Büyükakıllı¹,

Atıcı²,

Büyükdereli³

et al. 2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : Ne o na tal hypo xic-isc he mic (HI) in sult has acu te and long term de le te ri ous ef fects on many tis su es inc lu ding the pe rip he ral ner ves. To da te, no study has in ves ti ga ted the ro le of pla te let-ac ti va ting fac tor (PAF) an ta go nists on pe rip he ral ner ve da ma ge in a ne o na tal rat mo del of HI. In this study, we exa mi ned the ef fects of PAF an ta go nist (ABT-491) on pe rip he ral ner ve da ma ge in rats in the 16th we ek that we re ex po sed to HI on 7th day af ter birth. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : Se ven-day-old Wis tar rat pups we re sub jec ted to right com mon ca ro tid ar tery li ga ti on and hypo xi a (92% nit ro gen and 8% oxy gen) for one ho ur. They we re tre a ted eit her with ABT-491 (n=19) or sa li ne (n=20) im me di a tely af ter hypo xi a. In sham gro up (n=20), ne it her li ga ti on nor hypo xi a was per for med. The com po und mo tor ac ti on po ten ti al (CMAP) re cor dings of all ani mals we re ma de in the six te enth we ek fol lo wing the HI. For CMAP re cor dings, bi po lar sti mu la ting elec tro des we re pla ced on the sci a tic ner ve. Upon sti mu la ti on, two sur fa ce elec tro des, pla ced over the gas troc ne mi us musc le, re cor ded com po und musc le ac ti on po ten ti als. R Re e s su ul lt ts s: : The amp li tu de of CMAP re cor ded from the rats tre a ted with sa li ne af ter hypo xi a was smaller com pa red to the sham gro up. However, the CMAP re cor ded from the gro up tre a ted with ABT-491 af ter HI was not sig ni fi cantly dif fe rent from the sham gro up. C Co on nc c l lu u s si i o on n: : This study imp li es that HI has axo nal dama ge on pe rip he ral ner ve but a PAF an ta go nist ABT-491 has a pre ven ti ve ef fect on the axo nal dysfunc ti on af ter HI.K Ke ey y W Wo or rd ds s : : ABT-491; Action potentials; peripheral nerves; ischemia; anoxia Ö ÖZ ZE ET T A Am ma aç ç: : Ne o na tal hi pok sik-is ke mik (Hİ) ha sar pe ri fe rik si nir ler da hil bir çok do ku da kı sa ve uzun va de de za rar lı et ki ler gös te rir. Bu gü ne ka dar, Hİ 'ye ma ruz ka lan ye ni do ğan sı çan la rın pe rife rik si nir ha sa rı üze ri ne pla te let ak ti ve edi ci fak tör (PAF) an ta go nis ti nin ro lü araş tı rıl ma mış tır. Bu ça lış ma da PAF an ta go nis ti nin (ABT-491) do ğum dan son ra ki yedinci gün de Hİ' ye ma ruz ka lan sı -çan lar da 16. haf ta da ki pe ri fe rik si nir ha sa rı na et ki le ri ni in ce le dik. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Ye di gün-lük Wis tar sı çan yav ru la rı sağ or tak ka ro tid ar ter li gas yo nu na ve bir sa at sü rey le hi pok si ye (%92 nit ro jen ve %8 ok si jen) ma ruz bı ra kıl dı lar. Hi pok si nin he men ar dın dan bir grup sı ça na ABT-491 (ABT Gru bu), di ğer bir grup sı ça na se rum fiz yo lo jik (Sa li n Gru bu) ve ril di. Üçün cü grup sı ça na (Sham Gru bu) li gas yon ve ya hi pok si uy gu lan ma dı. Bü tün hay van lar da Hİ' yi iz le yen onal tın cı hafta da bi le şik mo tor ak ...

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mentioning

confidence: 99%

Protective Effects of Platelet-Activating Factor Antagonist ABT-491 on the Peripheral Nerves in Hypoxic Ischemia-Induced Neonatal Rat Model

Büyükakıllı¹,

Atıcı²,

Büyükdereli³

et al. 2011

Turkiye Klinikleri J Med Sci

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“…Studies showing that local injection of PAF to the periphery such as skin enhances pain sensitivity in animals [5][6][7] and humans 8) suggest that PAF is an important substrate in the formation of pain. The injection of lyso-PAF, which is a structurally-related, biologically-inactive form of PAF, failed to produce pain responses 6) and appeared to involve the specific target receptor, PAFR.…”

Section: Role Of Paf and Pafrmentioning

confidence: 99%

“…The injection of lyso-PAF, which is a structurally-related, biologically-inactive form of PAF, failed to produce pain responses 6) and appeared to involve the specific target receptor, PAFR. On the other hand, PAFR antagonists, such as BN52021, produced antinociceptive effects in a model of inflammatory pain evoked by tissue damage.…”

Section: Role Of Paf and Pafrmentioning

confidence: 99%

Platelet-Activating Factor and Pain

Tsuda

Tozaki‐Saitoh

Inoue

2011

Biological & Pharmaceutical Bulletin

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Platelet-activating factor (PAF) is a phospholipid mediator that regulates the functions of a variety of cells in the peripheral tissues and in the nervous system. Findings that injection of PAF exogenously at the skin or in the spinal cord induced pain hypersensitivity gave us much attention to its role in pain signaling. Studies using pharmacological and genetic tools to control the functions of the PAF receptor (PAFR) revealed that the PAF/PAFR system plays a role in tissue injury-induced pain, but not in the acute physiological pain evoked by thermal and mechanical stimuli. Recent investigations have focused on the roles of PAFR in pathological chronic pain such as the neuropathic pain that occurs after nerve injury for which there is currently no effective therapy. Nerve injury upregulated PAFRs in dorsal root ganglion (DRG) neurons. Studies using PAFR antagonists and PAFR-deficient mice indicated a crucial role of PAFR in production of tumor necrosis factor a a (TNFa a) and interleukin-1b b (IL-1b b) in the DRG and in developing and maintaining neuropathic pain. Thus, blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain.

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“…Local injection of PAF into the rat hindpaw increases the sensitivity to noxious stimulation (Bonnet et al. 1981; Belanger et al. 1987; Dallob et al.…”

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confidence: 99%

Reduced pain behaviors and extracellular signal‐related protein kinase activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet‐activating factor receptor

Tsuda

Ishii

Masuda

et al. 2007

Journal of Neurochemistry

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Peripheral tissue injury causes the release of various mediators from damaged and inflammatory cells, which in turn activates and sensitizes primary sensory neurons and thereby produces persistent pain. The present study investigated the role of platelet-activating factor (PAF), a phospholipid mediator, in pain signaling using mice lacking PAF receptor (pafr)/) mice). Here we show that pafr)/) mice displayed almost normal responses to thermal and mechanical stimuli but exhibit attenuated persistent pain behaviors resulting from tissue injury by locally injecting formalin at the periphery as well as capsaicin pain and visceral inflammatory pain without any alteration in cytoarchitectural or neurochemical properties in dorsal root ganglion (DRG) neurons and a defect in motor function. However, pafr)/) mice showed no alterations in spinal pain behaviors caused by intrathecally administering agonists for N-methyl-D-aspartate (NMDA) and neurokinin 1 receptors. A PAFR agonist evoked an intracellular Ca 2+ response predominantly in capsaicin-sensitive DRG neurons, an effect was not observed in pafr)/) mice. By contrast, the PAFR agonist did not affect C-or Ad-evoked excitatory postsynaptic currents in substantia gelatinosa neurons in the dorsal horn. Interestingly, mice lacking PAFR showed reduced phosphorylation of extracellular signal-related protein kinase (ERK), an important kinase for the sensitization of primary sensory neurons, in their DRG neurons after formalin injection. Furthermore, U0126, a specific inhibitor of the ERK pathway suppressed the persistent pain by formalin. Thus, PAFR may play an important role in both persistent pain and the sensitization of primary sensory neurons after tissue injury. Keywords: mitogen-activated protein kinase, platelet-activating factor receptor, primary afferent sensory neurons, tissue injury pain.

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L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-4-benzofuranol): a novel, selective, orally active 5-lipoxygenase inhibitor

Cited by 31 publications

References 23 publications

Protective Effects of Platelet-Activating Factor Antagonist ABT-491 on the Peripheral Nerves in Hypoxic Ischemia-Induced Neonatal Rat Model

Protective Effects of Platelet-Activating Factor Antagonist ABT-491 on the Peripheral Nerves in Hypoxic Ischemia-Induced Neonatal Rat Model

Platelet-Activating Factor and Pain

Reduced pain behaviors and extracellular signal‐related protein kinase activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet‐activating factor receptor

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