Plosker G L, Goa K L
Adis International Limited, Auckland, New Zealand.
Drugs. 1991 Nov;42(5):805-24. doi: 10.2165/00003495-199142050-00007.
Granisetron (BRL 43694) is a highly selective 5-HT3 receptor antagonist which possesses significant antiemetic activity, likely mediated through antagonism of 5-HT3 receptors on abdominal vagal afferents and possibly in or near the chemoreceptor trigger zone. Clinical trials in cancer patients demonstrate that, compared with placebo, granisetron significantly reduces the incidence of nausea and vomiting for 24 hours after administration of high-dose cisplatin. In large comparative trials, 70% of patients who received granisetron prior to cisplatin or other chemotherapy experienced complete inhibition of vomiting with little or no nausea for 24 hours after antineoplastic administration; these results were similar to those obtained with high-dose metoclopramide plus dexamethasone, and superior to a combination of chlorpromazine plus dexamethasone, or prochlorperazine plus dexamethasone, or methylprednisolone monotherapy. The most frequently reported adverse event associated with granisetron administration is headache which occurs in about 10 to 15% of patients while constipation, somnolence, diarrhoea and minor transient changes in blood pressure have been reported less frequently. Extrapyramidal effects, which can occur with high-dose metoclopramide and may be a limiting factor in its use, have not been noted with granisetron administration. Thus, granisetron is an effective, well tolerated and easily administered agent for the prophylaxis of nausea and vomiting induced by cancer chemotherapy which appears to be devoid of extrapyramidal side effects associated with metoclopramide. As a member of a new class of drugs, the selective 5-HT3 receptor antagonists, granisetron provides the medical oncologist with a new, potentially more acceptable antiemetic therapy.
格拉司琼（BRL 43694）是一种高度选择性的5-羟色胺3（5-HT3）受体拮抗剂，具有显著的止吐活性，其作用可能是通过拮抗腹部迷走神经传入纤维上的5-HT3受体，也可能是通过作用于化学感受器触发区或其附近的5-HT3受体介导的。癌症患者的临床试验表明，与安慰剂相比，格拉司琼能显著降低大剂量顺铂给药后24小时内恶心和呕吐的发生率。在大型对比试验中，70%在顺铂或其他化疗前接受格拉司琼治疗的患者在接受抗肿瘤药物治疗后24小时内呕吐完全得到抑制，几乎没有或仅有轻微恶心；这些结果与大剂量甲氧氯普胺加地塞米松治疗的结果相似，且优于氯丙嗪加地塞米松、或丙氯拉嗪加地塞米松、或甲泼尼龙单药治疗的结果。与格拉司琼给药相关的最常见不良事件是头痛，约10%至15%的患者会出现，而便秘、嗜睡、腹泻和血压轻微短暂变化的报告则较少。大剂量甲氧氯普胺可能出现的锥体外系反应是其使用的一个限制因素，但格拉司琼给药未出现此类反应。因此，格拉司琼是一种有效、耐受性良好且易于给药的药物，可用于预防癌症化疗引起的恶心和呕吐，且似乎没有与甲氧氯普胺相关的锥体外系副作用。作为一类新型药物——选择性5-HT3受体拮抗剂的成员，格拉司琼为肿瘤内科医生提供了一种新的、可能更易接受的止吐治疗方法。
