For the love of paradox: from neurobiology to pharmacology.
For the love of paradox: from neurobiology to pharmacology.
复制标题
对于悖论的热爱：从神经生物学到药理学。
DOI：
10.1097/fbp.0b013e328348ec6f
复制
发表时间：
2011
影响因子：
1.6
通讯作者：
Giles,Heather
中科院分区：
文献类型：
--
作者：
Bond,RichardA;Giles,Heather
某些药物的急性和慢性作用往往是相反的。例如，在充血性心力衰竭中，β-肾上腺素受体激动剂的急性给药可有益地改善疾病症状，但长期使用会增加死亡率。相反，某些β-肾上腺素受体拮抗剂/反向激动剂（β-受体阻滞剂）最初通过降低充血性心力衰竭的心肌收缩力引起有害反应，而用相同的β-受体阻滞剂长期治疗可改善收缩力和存活率。此外，这种时间依赖性的逆转结果发生在非药物干预中，如运动，甚至可以在植物对修剪或其他应激源的反应中观察到，结果是不同的短期与长期效应。在这里，我们回顾了这些现象，特别强调药理作用的时间分离。尽管弗朗西斯·科尔佩特利用这一知识领导了一个最初产生痛觉过敏的镇痛化合物的药物发现项目，但我们关注的是中枢神经系统以外的例子。
The acute and chronic effects of certain drugs can often be opposite. For example, in congestive heart failure acute administration of β-adrenoceptor agonists results in beneficial improvement in symptoms of the disease, but their chronic use increases mortality. Conversely, certain β-adrenoceptor antagonists/inverse agonists (β-blockers) initially cause a detrimental response by decreasing cardiac contractility in congestive heart failure, whereas chronic treatment with the same β-blockers improves contractility and survival. Furthermore, this time-dependent reversal of outcomes occurs in nonpharmacological interventions, such as exercise, and can even be observed in the response of plants to pruning or other stressors, with the results being a different short-term versus long-term effect. Here, we review some of these phenomena with a special emphasis on the temporal dissociation of pharmacological effects. Although Francis Colpaert used this knowledge to lead a drug discovery project for an analgesic compound that initially produced hyperalgesia, we focused on examples outside the central nervous system.