Alosetron

Alosetron · aloosetron. · GR-68755X · GR-68755 · ALOSETRON USP/EP/BP · Alosetron (GR-68755X · GR 68755 · GR 68755X

https://huagongshe.com/ko/chemical/2099

식별자 및 물리적 특성

CAS No.	122852-42-0
분자식	C17H18N4O
평균 분자량	294.35 g/mol
단동위원소 질량	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

화학 및 물리적 성질

XLogP	1.6
극성 표면적	53.9
수소 결합 공여자 수	1
수소 결합 수용자 수	2
회전 가능 결합 수	2
무거운 원자 수	22
형식 전하	0
복잡도	442
LogP(분배 계수)	2
용해도	4.38e-01 g/L에 용해됨DMSO
Physical Description	Solid
녹는점	238-240 °C
끓는 점	648.1±55.0 °C(Predicted)
밀도	1.34±0.1 g/cm3(Predicted)
저장 조건	Store at -20°C
물리적 상태	가루
pKa(산도 계수)	14.10±0.10(Predicted)

화학적 성질

crystalline powder

안전 및 규제

유해 작용	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.

유해 작용

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.

용도

Anti-emetic.