Humphrey P P, Bountra C, Clayton N, Kozlowski K
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, UK.
Aliment Pharmacol Ther. 1999 May;13 Suppl 2:31-8.
There is evidence from studies, in both animals and humans, that 5-HT3 receptor blockade has potential value in the treatment of irritable bowel syndrome, particularly in those patients with diarrhoea-predominant bowel habits. New findings suggest that 5-HT3 receptors exist on gut afferent neurones and that their activation by locally released 5-HT leads to visceral nociceptive stimulation, in addition to increased neuronally-mediated motor and secretory activity. If this concept is validated, it will provide a rationale for the use of 5-HT3 receptor antagonists in patients with increased gut motility, reduced fluid absorption and low nociceptive thresholds leading to abdominal pain. Alosetron is a highly selective, potent 5-HT3 receptor antagonist which is well absorbed with a long pharmacodynamic half-life. Its ability to provide long-lasting blockade of 5-HT3 receptors throughout the body make it an ideal candidate within its class to evaluate the clinical hypothesis that sustained and ubiquitous 5-HT3 receptor blockade is of value in the treatment of IBS.
动物和人体研究均有证据表明，5-羟色胺3（5-HT3）受体阻断剂在治疗肠易激综合征方面具有潜在价值，尤其是对那些以腹泻为主的肠易激综合征患者。新的研究结果表明，肠道传入神经元上存在5-HT3受体，局部释放的5-HT激活这些受体后，除了增加神经介导的运动和分泌活动外，还会导致内脏伤害性刺激。如果这一概念得到证实，将为5-HT3受体拮抗剂用于肠道蠕动增强、液体吸收减少且痛觉阈值低导致腹痛的患者提供理论依据。阿洛司琼是一种高度选择性、强效的5-HT3受体拮抗剂，吸收良好，药效学半衰期长。它能够在全身对5-HT3受体进行持久阻断，使其成为该类药物中评估“持续且广泛的5-HT3受体阻断对肠易激综合征治疗有价值”这一临床假设的理想候选药物。
