坦帕诺 (tenapanor)
坦帕诺 (tenapanor) 是一种新型的胃肠钠离子质子交换体 3 (NHE3) 的抑制剂，可减少膳食钠吸收，使更多的液体留在肠道，从而使粪便变得松软，缓解便秘。III 期试验正在进行中，[100]ClinicalTrials.gov. A 26-week study to evaluate the efficacy and safety of tenapanor in IBS-C (T3MPO-2). February 2017 [internet publication].https://clinicaltrials.gov/ct2/show/NCT02686138[101]ClinicalTrials.gov. A long-term safety study of tenapanor for the treatment of IBS-C (T3MPO-3). April 2016 [internet publication].https://clinicaltrials.gov/ct2/show/NCT02727751并且美国食品药品监督管理局 (FDA) 正在审查一项关于批准将其用于治疗肠易激综合征便秘患者的申请。
神经营养因子-3
神经营养因子-3（NT-3）促进感觉神经元的成熟并调制神经肌肉接头处的突触传递。[102]Chalazonitis A. Neurotrophin-3 in the development of the enteric nervous system. Prog Brain Res. 2004;146:243-63.http://www.ncbi.nlm.nih.gov/pubmed/14699968?tool=bestpractice.com 一项为期4周的针对107例中重度、依赖泻药或灌肠剂的慢传输型便秘（STC）患者的随机对照试验表明，NT-3增加了完全自发排便的次数、改善了粪便性状和排便费力并缩短了结肠传输时间。[103]Parkman HP, Rao SS, Reynolds JC, et al. Neurotrophin-3 improves functional constipation. Am J Gastroenterol. 2003 Jun;98(6):1338-47.http://www.ncbi.nlm.nih.gov/pubmed/12818279?tool=bestpractice.com
骶神经刺激（SNS）
研究表明SNS可能对便秘患者有益。[104]Dinning PG, Fuentealba SE, Kennedy ML, et al. Sacral nerve stimulation induces pan-colonic propagating pressure waves and increases defecation frequency in patients with slow-transit constipation. Colorectal Dis. 2007 Feb;9(2):123-32.http://www.ncbi.nlm.nih.gov/pubmed/17223936?tool=bestpractice.com[105]Holzer B, Rosen HR, Novi G, et al. Sacral nerve stimulation for neurogenic faecal incontinence. Br J Surg. 2007 Jun;94(6):749-53.http://www.ncbi.nlm.nih.gov/pubmed/17410558?tool=bestpractice.com[106]Malouf AJ, Wiesel PH, Nicholls T, et al. Short-term effects of sacral nerve stimulation for idiopathic slow transit constipation. World J Surg. 2002 Feb;26(2):166-70.http://www.ncbi.nlm.nih.gov/pubmed/11865344?tool=bestpractice.com[107]Dudding TC. Future indications for sacral nerve stimulation. Colorectal Dis. 2011;2011 Mar;13(suppl 2):23-8.http://www.ncbi.nlm.nih.gov/pubmed/21284799?tool=bestpractice.com[108]Maeda Y, Matzel K, Lundby L, et al. Postoperative issues of sacral nerve stimulation for fecal incontinence and constipation: a systematic literature review and treatment guideline. Dis Colon Rectum. 2011 Nov;54(11):1443-60.http://www.ncbi.nlm.nih.gov/pubmed/21979192?tool=bestpractice.com SNS改善肠道功能的机制尚不清楚，但是一项针对6例STC的患者的研究表明骶3神经根的刺激导致推进性收缩和高振幅推进性收缩的频率增加。[104]Dinning PG, Fuentealba SE, Kennedy ML, et al. Sacral nerve stimulation induces pan-colonic propagating pressure waves and increases defecation frequency in patients with slow-transit constipation. Colorectal Dis. 2007 Feb;9(2):123-32.http://www.ncbi.nlm.nih.gov/pubmed/17223936?tool=bestpractice.com
Naloxegol
两项双盲Ⅲ期试验研究了 naloxegol 的有效性和安全性，这是一种具有外周作用的 μ 阿片受体拮抗剂，用于治疗阿片诱发的便秘。[109]Chey WD, Webster L, Sostek M, et al. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014 Jun 19;370(25):2387-96.http://www.ncbi.nlm.nih.gov/pubmed/24896818?tool=bestpractice.com 两项研究均显示 naloxegol 组的反应率显著高于安慰剂组。在一项研究中，使用较低剂量 naloxegol 的治疗组患者中，反应率也较高。虽然 FDA 已批准将该药用于治疗慢性非癌症性疼痛患者中阿片受体激动剂诱发的便秘，但尚未在临床实践中常规使用。
Naldemedine
此药是一种外周性阿片受体拮抗剂，美国 FDA 已批准该药用于治疗慢性非癌症性疼痛患者中阿片诱发的便秘。 在存在阿片诱发的便秘的日本癌症患者中开展了一项随机 Ⅲ期临床试验，结果证明：与安慰剂相比，每周的自发排便次数显著改善。[110]Murata T, Katakami N, Harada T, et al. Treatment of opioid-induced constipation with naldemedine in patients with cancer: onset of action in a randomized phase 3 trial. Ann Oncol. 2016;27:1466P. 一项进一步的网络 Meta 分析报告称，与其他药物治疗相比，naldemedine 是阿片类药物所致便秘的最有效治疗药物。[111]Luthra P, Burr NE, Brenner DM, et al. Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis. Gut. 2018 May 5 [Epub ahead of print].http://www.ncbi.nlm.nih.gov/pubmed/29730600?tool=bestpractice.com
5-HT(4) 激动剂
Velusetrag 和 naronapride 是具有高度选择性的 5-HT(4) 激动剂，能够改善区域性胃肠道传输的所有组成部分，包括胃排空、小肠传输和结肠传输时间。[112]Manini ML, Camilleri M, Goldberg M, et al. Effects of velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation. Neurogastroenterol Motil. 2010 Jan;22(1):42-9, e7-8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905526/http://www.ncbi.nlm.nih.gov/pubmed/19691492?tool=bestpractice.com[113]Camilleri M, Vazquez-Roque MI, Burton D, et al. Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans. Neurogastroenterol Motil. 2007 Jan;19(1):30-8.http://www.ncbi.nlm.nih.gov/pubmed/17187586?tool=bestpractice.com 在 II 期临床试验中，这两种药物还被证实能够改善许多慢性特发性便秘患者的自发排便；然而，它们尚未上市。[114]Goldberg M, Li YP, Johanson JF, et al. Clinical trial: the efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation - a 4-week, randomized, double-blind, placebo-controlled, dose-response study. Aliment Pharmacol Ther. 2010 Nov;32(9):1102-12.http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2010.04456.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21039672?tool=bestpractice.com[115]Shin A, Camilleri M, Kolar G, et al. Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment Pharmacol Ther. 2014 Feb;39(3):239-53.http://onlinelibrary.wiley.com/doi/10.1111/apt.12571/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24308797?tool=bestpractice.com
吡苯氧磺钠
匹可硫酸钠是一种前体药物，经结肠菌群的脱硫作用转化为有活性的泻药分子。虽然已经使用许多年，但最近一项随机对照试验才证实该药对慢性便秘的有效性。完全自主排便的增加：有高质量的研究证实吡苯氧磺钠与完全自主排便的增加有关，其可使排便增加至3.4次/周而安慰机组为1.7次/周。 大约70%的患者在首剂24小时内出现完全自主排便。[116]Mueller-Lissner S, Kamm MA, Wald A, et al. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation. Am J Gastroenterol. 2010;105:897-903.http://www.ncbi.nlm.nih.gov/pubmed/20179697?tool=bestpractice.com系统评价或者受试者＞200名的随机对照临床试验（RCT）。
