共 40 条
The cyclooxygenase-2 inhibitor GW406381X [2-(4-ethoxyphenyl)-3-[4-(methylsulfonyl)phenyl]-pyrazolo[ 1,5-b]pyridazine] is effective in animal models of neuropathic pain and central sensitization
被引:53
作者:

Bingham, S
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Beswick, PJ
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Bountra, C
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Brown, T
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Campbell, IB
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Chessell, IP
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Clayton, N
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Collins, SD
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Davey, PT
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Goodland, H
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Gray, N
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Haslam, C
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Hatcher, JP
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Hunter, AJ
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Lucas, F
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h-index: 0
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GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Murkitt, G
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Naylor, A
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Pickup, E
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Sargent, B
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Summerfield, SG
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Stevens, A
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Stratton, SC
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England

Wiseman, J
论文数: 0 引用数: 0
h-index: 0
机构:
GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England
机构:
[1] GlaxoSmithKline Pharmaceut, Pain Res Dept, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England
关键词:
D O I:
10.1124/jpet.104.075267
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
The pathogenic form of the cyclooxygenase ( COX) enzyme, COX-2, is also constitutively present in the spinal cord and has been implicated in chronic pain states in rat and man. A number of COX-2 inhibitors, including celecoxib and rofecoxib, are already used in man for the treatment of inflammatory pain. Preclinically, the dual-acting COX-2 inhibitor, GW406381X [2-(4-ethoxyphenyl)-3-[4-(methylsulfonyl)phenyl]-pyrazolo[1,5-b]pyridazine, where X denotes the free base], is as effective as rofecoxib and celecoxib in the rat established Freund's Complete Adjuvant model with an ED50 of 1.5 mg/kg p.o. compared with 1.0 mg/kg p.o. for rofecoxib and 6.6 mg/kg p.o. for celecoxib. However, in contrast to celecoxib (5 mg/kg p.o.b.i.d.) and rofecoxib (5 mg/kg p.o.b.i.d.), which were without significant effect, GW406381X (5 mg/kg p.o. b.i.d.) fully reversed mechanical allodynia in the chronic constriction injury model and reversed thermal hyperalgesia in the mouse partial ligation model, both models of neuropathic pain. GW406381X, was also effective in a rat model of capsaicin-induced central sensitization, when given intrathecally (ED50 = 0.07 mug) and after chronic but not acute oral dosing. Celecoxib and rofecoxib had no effect in this model. Several hypotheses have been proposed to try to explain these differences in efficacy, including central nervous system penetration, enzyme kinetics, and potency. The novel finding of effectiveness of GW406381X in these models of neuropathic pain/central sensitization, in addition to activity in inflammatory pain models and together with its central efficacy, suggests dual activity of GW406381X compared with celecoxib and rofecoxib, which may translate into greater efficacy in a broader spectrum of pain states in the clinic.
引用
收藏
页码:1161 / 1169
页数:9
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