Novel pharmacology: asimadoline, a kappa-opioid agonist, and visceral sensation.
Novel pharmacology: asimadoline, a kappa-opioid agonist, and visceral sensation.
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DOI：
10.1111/j.1365-2982.2008.01183.x
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发表时间：
2008-09
影响因子：
3.5
通讯作者：
Camilleri M
中科院分区：
文献类型：
--
作者：
Camilleri M
阿西马多林是一种有效的κ-阿片受体激动剂，具有二芳基乙酰胺结构。它对κ受体具有高亲和力，IC 50为5.6 nM（豚鼠）和1.2 nM（人重组体），对人重组受体具有高选择性，κ：μ：δ结合比为1：501：498。在体外试验中，其作为完全激动剂发挥作用。在健康志愿者和肠易激综合征患者中，阿西马多林降低了对亚伤害性压力下结肠扩张的感觉，而不改变结肠顺应性。阿西马多林降低饱腹感并增加餐后胃容量（女性志愿者）。然而，对胃肠道传输、结肠顺应性、空腹或餐后结肠张力无显著影响。在40例功能性消化不良患者的临床试验中（罗马II），阿西马多林在8周内没有显著改变饱食或症状。然而，阿西马多林，0.5毫克，显着降低饱食的患者较高的餐后饱食评分，和每日餐后饱食的严重程度（超过8周）;阿西马多林1.0毫克组是边界显着。在IBS患者的临床试验中，使用asimadoline按需治疗后2小时的平均疼痛没有显著减少。事后分析表明，阿西马多林是有效的混合型IBS。在596例患者中进行的一项为期12周的研究中，使用0.5 mg和1.0 mg阿西马多林长期治疗与IBS-D患者的疼痛和不适充分缓解、疼痛评分改善和无疼痛天数相关。1.0 mg剂量在IBS交替中也有效。也有几周排便频率和尿急显著减少。迄今为止，阿西马多林在人体试验中耐受性良好。
Asimadoline is a potent κ-opioid receptor agonist with a diaryl acetamide structure. It has high affinity for the κ receptor, with IC50 of 5.6 nM (guinea pig) and 1.2 nM (human recombinant), and high selectively with κ: μ: δ binding ratios of 1:501:498 in human recombinant receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in IBS patients without alteration of colonic compliance. Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II), asimadoline did not significantly alter satiation or symptoms over 8 weeks. However, asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average pain 2 hours post-on-demand treatment with asimadoline was not significantly reduced. Post-hoc analyses suggest asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with asimadoline, 0.5 mg and 1.0 mg, was associated with adequate relief of pain and discomfort, improvement in pain score and number of pain free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency. Asimadoline has been well tolerated in human trials to date.
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影响因子：
7.3
作者：
BARBER, A;BARTOSZYK, GD;SEYFRIED, CA
通讯作者：
SEYFRIED, CA
影响因子：
4.8
作者：
Chesterfield, Matthew;Janik, James;Callahan, Phyllis
通讯作者：
Callahan, Phyllis
影响因子：
3.4
作者：
Binder, W;Scott, C;Walker, JS
通讯作者：
Walker, JS
影响因子：
3.1
作者：
Coruzzi, G;Morini, G;Bertaccini, G
通讯作者：
Bertaccini, G
影响因子：
5
作者：
DIOP, L;RIVIERE, PJM;JUNIEN, JL
通讯作者：
JUNIEN, JL