Petroianu Georg A, Lorke Dietrich E
College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates.
Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States.
Front Neurosci. 2020 Jul 16;14:629. doi: 10.3389/fnins.2020.00629. eCollection 2020.
The use of dopamine receptor blockers for chronic singultus treatment is based-at least partially-on circular thinking: chlorpromazine is FDA-approved for hiccups, chlorpromazine is a neuroleptic, neuroleptics are dopamine receptor blockers, and therefore hiccup is due to dopaminergic dysfunction. Chlorpromazine interacts with high affinity with a multitude of receptors and ion channels. This promiscuity is the basis for many of the therapeutic effects and adverse drug reactions of this drug. While an involvement of dopamine is certain, it is by no means clear that dopaminergic dysfunction is the hallmark of singultus. The common denominator of most remedies for transient hiccup is their ability to activate the vagus nerve. Both afferent and efferent vagal activity and the central integration of the Xth cranial nerve function are modulated, inter alia, via serotonergic mechanisms; beneficial (therapeutic) effects for hiccup are to be expected from serotonin (5-HT) receptor subtype ligands that enhance vagal activity. Taken together, it appears that the ability to increase vagus output is mainly associated with 5-HT, 5-HT, and 5-HT agonists and with 5-HT antagonists. The plausibility of the serotonergic singultus hypothesis is examined against available pharmacokinetic, pharmacodynamic, and clinical data for a number of drugs.
氯丙嗪被美国食品药品监督管理局（FDA）批准用于治疗打嗝，氯丙嗪是一种抗精神病药物，抗精神病药物是多巴胺受体阻滞剂，因此打嗝是由于多巴胺能功能障碍所致。氯丙嗪能与多种受体和离子通道高亲和力结合。这种多效性是该药物许多治疗作用和药物不良反应的基础。虽然多巴胺参与其中是确定的，但多巴胺能功能障碍是否是呃逆的标志一点也不清楚。大多数治疗短暂呃逆的药物的共同特点是它们激活迷走神经的能力。迷走神经的传入和传出活动以及第十对脑神经功能的中枢整合尤其通过血清素能机制进行调节；预计血清素（5-HT）受体亚型配体增强迷走神经活动对呃逆有有益（治疗）作用。综上所述，似乎增加迷走神经输出的能力主要与5-HT、5-HT和5-HT激动剂以及5-HT拮抗剂有关。根据多种药物的现有药代动力学、药效学和临床数据，对血清素能呃逆假说的合理性进行了检验。
