化工社化工社 化学情報印刷レポート · 研究参考用
アロセトロン
アロセトロン · 5-メチル-2-[(5-メチル-1H-イミダゾール-4-イル)メチル]-1H,2H,3H,4H,5H-ピリド[4,3-b]インドール-1-オン · 3,4-ジヒドロ-5-メチル-2-[(5-メチル-1H-イミダゾール-4-イル)メチル]-5H-ピリド[4,3-b]インドール-1(2H)-オン · 2,3,4,5-テトラヒドロ-5-メチル-2-[(5-メチル-1H-イミダゾール-4-イル)メチル]-1H-ピリド[4,3-b]インドール-1-オン · 2-[(5-メチル-1H-イミダゾール-4-イル)メチル]-5-メチル-3,4-ジヒドロ-γ-カルボリン-1(2H)-オン · Alosetron · aloosetron. · GR-68755X
識別子と物理属性
| CAS No. | 122852-42-0 |
|---|---|
| 分子式 | C17H18N4O |
| 平均分子量 | 294.35 g/mol |
| 単同位体質量 | 294.14806121 g/mol |
| SMILES | Cc1[nH]cnc1CN1CCc2c(c3ccccc3n2C)C1=O |
| InChIKey | JSWZEAMFRNKZNL-UHFFFAOYSA-N |
| PubChem CID | 2099 |
| ChEMBL | CHEMBL1110 |
| ChEBI | CHEBI:253342 |
| DTXSID | DTXSID6044278 |
| 現地名 | アロセトロン |
化学・物理的性質
| XLogP | 1.6 |
|---|---|
| 極性表面積 | 53.9 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 2 |
| 回転可能結合数 | 2 |
| 重原子数 | 22 |
| 形式電荷 | 0 |
| 複雑度 | 442 |
| LogP（分配係数） | 2 |
| 溶解度 | 4.38e-01 g/LDMSO |
| Physical Description | Solid |
| 融点 | 238-240 °C |
| 沸点 | 648.1±55.0 °C(Predicted) |
| 密度 | 1.34±0.1 g/cm3(Predicted) |
| 貯蔵条件 | Store at -20°C |
| 外観・状態 | Powder |
| pKa（酸解離定数） | 14.10±0.10(Predicted) |
化学的特性
crystalline powder
安全性と法規制
| 有害作用 | The most common adverse effect associated with alosetron administration is constipation. A randomized, double-blind, placebo-controlled study assessed the efficacy and safety of alosetron 0.5 mg and 1 mg in women with severe IBS-D. The study data revealed that constipation occurred in patients receiving 0.5 mg (9%), 1 mg once daily (16%), and 1 mg twice daily (19%).Other common adverse effects associated with alosetron therapy include:* Abdominal discomfort and pain* Nausea* Abdominal distension* Regurgitation and reflux* Hemorrhoids* Headache* FatigueAlthough rare, ischemic colitis has been reported in patients taking alosetron to treat IBS. Clinical trials comparing patients receiving alosetron 1 mg twice daily to patients receiving placebo showed that the cumulative incidence of ischemic colitis was 0.2% within the first 3 months and 0.3% within the first 6 months. A statistically significant increase in the incidence of ischemic colitis was observed in the pooled data of clinical trials involving patients receiving alosetron compared with placebo (0.15% vs 0.00%, p=0.03). No precise mechanism for this observation is known, but many have been hypothesized. One possible mechanism involves the blockade of 5-HT3 receptors, increasing free serotonin available to stimulate other serotonin receptors (ie, 5-HT1 and 5-HT2) that may be involved in vasoconstriction. This vasoconstriction may increase the risk of developing ischemic colitis in patients with concomitant atherosclerotic disease in vessels feeding the GI tract. Another hypothesis postulates that ischemic colitis may result from alosetron's effects on colonic motility and intestinal blood flow. Because alosetron is associated with severe constipation, patients with existing vascular disease may be at increased risk of developing intestinal ischemia. These predictions are based on observations of animal models and have not been studied in humans.Gastrointestinal adverse reactions are common in postmarketing surveillance studies. GI perforation, impaction, ulceration, small bowel mesenteric ischemia, headache, and skin rash have been reported in patients receiving alosetron.Drug-Drug Interactions* CYP1A2 inhibitors: Fluvoxamine, a potent CYP1A2 inhibitor, can inhibit the metabolism of alosetron if coadministered, leading to alosetron toxicity. Fluvoxamine can increase the mean plasma concentration of alosetron by 6-fold and prolong the half-life by 3-fold. Moderate CYP1A2 inhibitors (eg, cimetidine, quinolone antibiotics) should be avoided unless clinically indicated.* CYP3A4 inhibitors: Ketoconazole, clarithromycin, telithromycin, voriconazole, itraconazole, and protease inhibitors are strong CYP3A4 inhibitors and may increase alosetron toxicity. Due to potential drug interactions, clinicians should exercise caution when administering alosetron and CYP3A4 inhibitors concomitantly. |
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用途
使用
Anti-emetic.