Martin-Jimenez M, Diaz-Rubio E, Sangro B
Servicio de Oncología Médica, Hospital Universitario San Carlos, Madrid, Spain.
Tumori. 1987 Oct 31;73(5):499-504. doi: 10.1177/030089168707300512.
A group of 132 patients with different disseminated solid tumors entered two consecutive antiemetic trials in which 5-fluorouracil given in a 120-h continuous infusion was the emetogenic stimulus. The purpose of the trials was to investigate the validity of Peroutka and Snyder's hypothesis. These authors suggested that CNS receptors other than the classical dopamine D-2 (e.g., histamine H-1 and muscarinic cholinergic receptors) were involved in emetic response. Hence, a combination of a phenothiazine (an antidopaminergic drug) with an antihistaminic or a tricyclic antidepressant (H-1 and muscarinic cholinergic blockers) was suggested to be possibly superior to phenothiazine alone against antineoplastic chemotherapy-induced vomiting. The first study showed the antiemetic superiority of a phenothiazine (thiethylperazine) over placebo but failed to show a superiority of the combination of thiethylperazine and an antihistaminic (diphenhydramine) over thiethylperazine alone. In contrast, the second study proved the superiority of the combination of thiethylperazine and a tricyclic antidepressant (amitriptyline) over thiethylperazine alone. In conclusion, tricyclic antidepressants - but not antihistaminics - potentiate the antiemetic activity of thiethylperazine against 5-fluorouracil-induced vomiting.
132名患有不同播散性实体瘤的患者参加了两项连续的止吐试验，试验中120小时持续输注5-氟尿嘧啶作为致吐刺激物。试验目的是研究佩鲁特卡和斯奈德假说的有效性。这些作者认为，除了经典的多巴胺D-2受体（如组胺H-1和毒蕈碱胆碱能受体）外，中枢神经系统受体也参与呕吐反应。因此，有人提出将吩噻嗪（一种抗多巴胺能药物）与抗组胺药或三环类抗抑郁药（H-1和毒蕈碱胆碱能阻滞剂）联合使用，可能比单独使用吩噻嗪更能有效对抗抗肿瘤化疗引起的呕吐。第一项研究显示，吩噻嗪（硫乙拉嗪）的止吐效果优于安慰剂，但未显示硫乙拉嗪与抗组胺药（苯海拉明）联合使用比单独使用硫乙拉嗪更具优势。相比之下，第二项研究证明硫乙拉嗪与三环类抗抑郁药（阿米替林）联合使用比单独使用硫乙拉嗪更具优势。总之，三环类抗抑郁药而非抗组胺药可增强硫乙拉嗪对5-氟尿嘧啶所致呕吐的止吐活性。
