New Developments in Prokinetic Therapy for Gastric Motility Disorders.
New Developments in Prokinetic Therapy for Gastric Motility Disorders.
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DOI：
10.3389/fphar.2021.711500
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发表时间：
2021
影响因子：
5.6
通讯作者：
Atieh J
中科院分区：
文献类型：
--
作者：
Camilleri M;Atieh J
促动力剂放大并协调胃肠肌肉收缩以促进腔内内容物的转运。根据饮食建议，促动力剂是第一种药物，其目标是改善胃排空和缓解胃轻瘫症状。由于可逆或不可逆的锥体外系震颤的风险，目前在美国唯一获批的胃轻瘫药物甲氧氯普胺的推荐使用时间少于3个月。多潘立酮是一种多巴胺D2受体拮抗剂，可通过FDA的扩大研究药物使用计划获得处方。大环内酯类药物是超说明书使用的，与快速耐受和不同的疗效持续时间有关。阿瑞匹坦可以缓解胃轻瘫的一些症状。目前正在开发针对不同胃（胃底、胃窦和幽门）运动功能的新型药物，包括新型多巴胺能5-HT 4激动剂、多巴胺能D2/3拮抗剂、神经激肽NK 1拮抗剂和生长激素释放肽激动剂。具有改善胃运动功能潜力的新靶点包括幽门、巨噬细胞/炎症功能、氧化应激和神经发生。在目前的审查中，我们讨论了使用药理学的方法，有可能提高运动功能的胃轻瘫的管理。
Prokinetic agents amplify and coordinate the gastrointestinal muscular contractions to facilitate the transit of intra-luminal content. Following the institution of dietary recommendations, prokinetics are the first medications whose goal is to improve gastric emptying and relieve symptoms of gastroparesis. The recommended use of metoclopramide, the only currently approved medication for gastroparesis in the United States, is for a duration of less than 3 months, due to the risk of reversible or irreversible extrapyramidal tremors. Domperidone, a dopamine D2 receptor antagonist, is available for prescription through the FDA’s program for Expanded Access to Investigational Drugs. Macrolides are used off label and are associated with tachyphylaxis and variable duration of efficacy. Aprepitant relieves some symptoms of gastroparesis. There are newer agents in the pipeline targeting diverse gastric (fundic, antral and pyloric) motor functions, including novel serotonergic 5-HT4 agonists, dopaminergic D2/3 antagonists, neurokinin NK1 antagonists, and ghrelin agonist. Novel targets with potential to improve gastric motor functions include the pylorus, macrophage/inflammatory function, oxidative stress, and neurogenesis. In the current review, we discuss the use of pharmacological approaches with potential to enhance motor functions in the management of gastroparesis.