NK1 (substance P) receptor antagonists -: why are they not analgesic in humans?
NK1 (substance P) receptor antagonists -: why are they not analgesic in humans?
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DOI：
10.1016/s0165-6147(00)01502-9
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发表时间：
2000-07-01
影响因子：
13.8
通讯作者：
Hill, R
中科院分区：
文献类型：
--
作者：
Hill, R
速激肽NK(1)受体拮抗剂在多种临床疼痛状态的临床试验中未能表现出疗效。相比之下，在动物临床前研究中，NK(1) 受体拮抗剂已被证明可以减弱炎症或神经损伤引起的伤害性反应，尽管它们对基线伤害性感受影响不大。在动物试验中具有这种活性的其他药物，通常是非甾体抗炎药 (NSAID)，对人类具有镇痛作用。因此，NK(1)受体拮抗剂似乎能够在动物试验中可检测到的水平上阻断对有害和其他应激性感觉刺激的行为反应，但无法提供在人类中产生临床镇痛所需的感觉阻断水平。
Tachykinin NK(1) receptor antagonists have failed to exhibit efficacy in clinical trials of a variety of clinical pain states. By contrast, in preclinical studies in animals NK(1) receptor antagonists have been shown to attenuate nociceptive responses sensitized by inflammation or nerve damage, although they exhibit little effect on baseline nociception. Other agents with this profile of activity in animal tests, typically nonsteroidal anti-inflammatory drugs (NSAIDs), are analgesic in humans. Thus, NK(1) receptor antagonists appear able to block behavioural responses to noxious and other stressful sensory stimuli at a level detectable in animal tests but fail to provide the level of sensory blockade required to produce clinical analgesia in humans.