PDF(Pubmed)
Abstract：
Nausea and vomiting are primitive aspects of mammalian physiology and behavior that ensure survival. Unfortunately, both are ubiquitously present side effects of drug treatments for many chronic diseases with negative consequences on pharmacotherapy tolerance, quality of life, and prognosis. One of the most critical clinical examples is the profound emesis and nausea that occur in patients undergoing chemotherapy, which continue to be among the most distressing side effects, even with the use of modern antiemetic medications. Similarly, antiobesity/diabetes medications that target the glucagon-like peptide-1 system, despite their remarkable metabolic success, also cause nausea and vomiting in a significant number of patients. These side effects hinder the ability to administer higher dosages for optimal glycemic and weight management and represent the major reasons for treatment discontinuation. Our inability to effectively control these side effects highlights the need to anatomically, molecularly, and functionally characterize novel neural substrates that drive and inhibit nausea and emesis. Here, we discuss clinical and preclinical evidence that highlights the glucose-dependent insulinotropic peptide receptor system as a novel therapeutic central target for the management of nausea and emesis.
摘要：
恶心和呕吐是确保生存的哺乳动物生理和行为的原始方面。不幸的是,两者都普遍存在许多慢性疾病的药物治疗副作用，对药物治疗耐受性有负面影响，生活质量,和预后。最关键的临床例子之一是接受化疗的患者会出现严重的呕吐和恶心，这仍然是最令人痛苦的副作用之一，即使使用现代止吐药物。同样，针对胰高血糖素样肽-1（GLP-1）系统的抗肥胖/糖尿病药物，尽管他们显著的代谢成功，也会导致大量患者恶心和呕吐。这些副作用掩盖了为了最佳的血糖和体重管理而施用更高剂量的能力,并且代表了治疗停止的主要原因。我们无法有效控制这些副作用突出了在解剖学上，分子，并在功能上表征驱动和抑制恶心和呕吐的新型神经基质。这里,我们讨论了临床和临床前证据,这些证据突出了葡萄糖依赖性促胰岛素分泌肽受体(GIPR)系统作为治疗恶心和呕吐的新型治疗中心靶点.
