RAMOSETRON HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H17N3O.ClH
Molecular Weight	315.797
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CN1C=C(C(=O)[C@@H]2CCC3=C(C2)N=CN3)C4=C1C=CC=C4

InChI

InChIKey=XIXYTCLDXQRHJO-RFVHGSKJSA-N

InChI=1S/C17H17N3O.ClH/c1-20-9-13(12-4-2-3-5-16(12)20)17(21)11-6-7-14-15(8-11)19-10-18-14;/h2-5,9-11H,6-8H2,1H3,(H,18,19);1H/t11-;/m1./s1

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB09290
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21146988 | https://www.ncbi.nlm.nih.gov/pubmed/12195819 | https://www.ncbi.nlm.nih.gov/pubmed/25949526

Ramosetron (INN) is a serotonin 5-HT3 receptor antagonist for the treatment of nausea, vomiting. And "diarrhea-predominant irritable bowel syndrome in males" (IBS-D). Ramosetron is licensed for use in India, Japan (Iribo) and selected Southeast Asian countries. In animal studies, ramosetron reduced defecation induced by corticotrophin-releasing hormone and had inhibitory effects on colonic nociception. In two randomized controlled studies including 957 patients with IBS-D, ramosetron increased monthly responder rates of patient-reported global assessment of IBS symptom relief compared with placebo. Ramosetron was also as effective as mebeverine in male patients with IBS-D. In a recent randomized controlled trial with 343 male patients with IBS-D, ramosetron has proved effective in improving stool consistency, relieving abdominal pain/discomfort, and improving health-related quality of life. Regarding safety, ramosetron is associated with a lower incidence of constipation compared with other 5-HT3 receptor antagonists and has not been associated with ischemic colitis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 3a (5-HT3a) receptor 48 Target ID: CHEMBL1899 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21146988	Antagonist 2849		0.06 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Chemotherapy induced nausea and vomiting 10 Sources: http://www.mims.com/india/drug/info/ramosetron?type=full&mtype=generic	Primary	Approved 8583	Iribo Approved Use Unknown
Postoperative nausea and vomiting 31 Sources: https://clinicaltrials.gov/ct2/show/NCT02849483	Primary	Phase IV 63	Iribo Approved Use Unknown
Irritable bowel syndrome 61 Sources: http://www.mims.com/india/drug/info/ramosetron?type=full&mtype=generic	Primary	Approved 8583	Iribo Approved Use Unknown

C_max

Value	Dose	Analyte	Population
18.5 pg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=20 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
27.4 pg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=20 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
23.3 pg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=16 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=10 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=47	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
23.3 pg/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=16 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=10 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=47	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2.39 pg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.79 pg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.42 pg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
125.3 pg × h/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=20 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
215.9 pg × h/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=20 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
151.8 pg × h/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=16 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=10 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=47	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
160.6 pg × h/mL OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=16 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=10 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=47	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
11.92 pg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
12.15 pg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
11 pg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
5.7 h OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=20 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.2 h OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=20 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.6 h OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=16 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=10 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=47	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.1 h OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=16 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K105_1.pdf#page=10 \| https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=47	5 μg single, oral dose: 5 μg route of administration: Oral experiment type: SINGLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4.09 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.8 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.75 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/800126_2399014F1026_1_016_1F.pdf#page=44	0.6 mg 2 times / day multiple, oral dose: 0.6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAMOSETRON plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
8.5% OTHER GOV'T https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=16 \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K101_1.pdf#page=6			RAMOSETRON plasma	Homo sapiens

Doses

Dose	Population	Adverse events
0.3 mg single, intravenous Recommended Dose: 0.3 mg Route: intravenous Route: single Dose: 0.3 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12166337/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12166337/	Sources: https://pubmed.ncbi.nlm.nih.gov/12166337/
5 ug 1 times / day multiple, oral Studied dose Dose: 5 ug, 1 times / day Route: oral Route: multiple Dose: 5 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21920001/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/21920001/	Disc. AE: Constipation... AEs leading to discontinuation/dose reduction: Constipation (grade 1-2, 1.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/21920001/

AEs

AE	Significance	Dose	Population
Constipation	grade 1-2, 1.7% Disc. AE	5 ug 1 times / day multiple, oral Studied dose Dose: 5 ug, 1 times / day Route: oral Route: multiple Dose: 5 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21920001/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/21920001/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 150 inhibitor 2252	activator 23 inhibitor 2438	activator 25 substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP2B6 926 CYP2C8 1057 CYP1A2 2153 P-gp 1741 CYP2E1 1060	CYP1A2 1197 P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2B6 1160	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K101_1.pdf Page: 9.0	no [IC50 >250 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K101_1.pdf Page: 9.0	no [IC50 >250 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/ \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_K101_1.pdf#page=9	no [IC50 >250 uM]
CYP1A2 2333	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/	no
CYP2C19 2141	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/	no
CYP2C9 2497	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/	no
CYP2D6 2546	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/	no
CYP2E1 1146	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/	no
CYP3A4 2633	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/	no
P-gp 1932	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf Page: 17.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/	weak [IC50 14.63 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/ \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17	weak [IC50 47.28 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/ \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17	weak [IC50 58.85 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/ \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17	weak [IC50 71.53 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16946512/ \| https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf#page=17	weak [IC50 >250 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18401578/	yes
P-gp 2052	substrate 4014 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE2NDM4OTUifX0=	yes
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18401578/	yes	weak (co-administration study) Comment: Paroxetine increased Ramosetron AUCinf by 1.14-fold and Cmax by 1.06-fold. Sources: https://pubmed.ncbi.nlm.nih.gov/18401578/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.pmda.go.jp/drugs/2008/P200800026/80012600_22000AMX01708_A100_1.pdf Page: 14.0

PubMed

Title	Date	PubMed
Evaluation of the pharmacological profile of ramosetron, a novel therapeutic agent for irritable bowel syndrome.	2007 Jul	17652911
Population pharmacokinetics of ramosetron.	2016 Feb	26558626

Patents

Sample Use Guides

In Vivo Use Guide

For treatment Nausea and vomiting associated with cancer chemotherapy in Adult: PO 100 mcg once daily. IV 300 mcg once daily. May administer an additional dose of 300 mcg if necessary. Max: 600 mcg/day. For treatment Irritable bowel syndrome in men PO 5 mcg once daily, may adjust dose according to symptoms. Max: 10 mcg/day.

Route of Administration: Other

In Vitro Use Guide

Mouse L cells and LV500 cells were washed three times with 1.0 mL of incubation buffer (composition (mm ): 141 NaCl, 4 KCl, 2.8 CaCl2, 1MgSO4, 10 d -glucose, 10 HEPES, pH 7.4).We used the same incubation buffer in the uptake study in all the cell lines. The uptake study was initiated by adding 250 L to multidishes of incubation buffer containing [14C]ramosetron (10 m ) or [3H]vinblastine (30 nm ) in the absence or presence of verapamil (10, 50 and 100 m ) or ciclosporin (20 m ). The cells were incubated at 37° C for a specified time. After incubation, the cells were washed three times with 1.0 mL of ice-cold incubation buffer to terminate the uptake. The cells were solubilized with 3 m NaOH and neutralized with 6 m HCl. [14C]ramosetron or [3H]vinblastine was measured by liquid scintillation counting after addition of scintillation fluid.

Name

Type

Language

RAMOSETRON HYDROCHLORIDE

Common Name

English

IRRIBOW

Preferred Name

English

Ramosetron hydrochloride [WHO-DD]

Common Name

English

RAMOSETRON HYDROCHLORIDE [MI]

Common Name

English

(-)-(R)-5-((1-METHYL-1H-INDOL-3-YL)CARBONYL)-4,5,6,7-TETRAHYDRO-1H-BENZIMIDAZOLE MONOHYDROCHLORIDE

Systematic Name

English

YM060

Code

English

METHANONE, (1-METHYL-1H-INDOL-3-YL)((6R)-4,5,6,7-TETRAHYDRO-1H-BENZIMIDAZOL-6-YL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

YM-060

Code

English

RAMOSETRON HYDROCHLORIDE [MART.]

Common Name

English

RAMOSETRON HYDROCHLORIDE [JAN]

Common Name

English

(R)-(-)-RAMOSETRON HYDROCHLORIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94726