HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Alosetron
Alosetron · aloosetron. · GR-68755X · GR-68755 · ALOSETRON USP/EP/BP · Alosetron (GR-68755X · GR 68755 · GR 68755X
Identifikatoren & physikalische Daten
| CAS No. | 122852-42-0 |
|---|---|
| Summenformel | C17H18N4O |
| Durchschnittliche Molmasse | 294,35 g/mol |
| Monoisotopische Masse | 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 |
Chemische & physikalische Eigenschaften
| XLogP | 1,6 |
|---|---|
| Polarare Oberfläche (TPSA) | 53,9 |
| H-Brücken-Donoren | 1 |
| H-Brücken-Akzeptoren | 2 |
| Frei drehbare Bindungen | 2 |
| Schwere Atome | 22 |
| Formalladung | 0 |
| Komplexität | 442 |
| LogP (Verteilungskoeffizient) | 2 |
| Löslichkeit | 4.38e-01 g/LDMSO |
| Physical Description | Solid |
| Schmelzpunkt | 238-240 °C |
| Siedepunkt | 648.1±55.0 °C(Predicted) |
| Dichte | 1.34±0.1 g/cm3(Predicted) |
| Lagerbedingungen | Store at -20°C |
| Aggregatzustand | Powder |
| pKa (Säurekonstante) | 14.10±0.10(Predicted) |
Sicherheit & Vorschriften
| Unerwünschte Wirkungen | 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. |
|---|---|
| Toxizitätsübersicht | Signs and Symptoms of OverdoseDuring clinical studies, doses up to 16 mg (8 times the recommended daily dose) have been administered without significant adverse reactions.Management of OverdoseThere is no specific antidote for alosetron. Patients should be managed with appropriate supportive therapy. Overdose with alosetron may reduce the first-pass metabolism of other drugs. A poison control center should be contacted for overdose treatment protocol. |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)alosetronDILI PositiveOralDOI:10.1016/j.drudis.2019.09.022 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during LactationNo information is available on the use of alosetron during breastfeeding. Because of relatively high protein binding and only moderate bioavailability, exposure of the breastfed infant is likely to be low. Until more data are available, alosetron should only be used with careful infant monitoring during breastfeeding.◉ Effects in Breastfed InfantsRelevant published information was not found as of the revision date.◉ Effects on Lactation and Breastmilk |
| R-Sätze (R) | 36/37/38 |
| Gefahrensymbole | Xi |
| Sicherheitshinweise (S) | 26-36 |
Anwendungen & Verwendung
Verwenden
Anti-emetic.