Details of the Drug

General Information of Drug (ID: DML2A03)

Drug Name

Alosetron

Synonyms

Lotronex; Lotrpnex; ALOSETRON HYDROCHLORIDE; Alosetron HCl; Alosetron hydrochloride [USAN]; Alosetron monohydrochloride; GR 68755; GR 68755X; GR 68755c; GR68755; Alosetron (INN); Alosetron [INN:BAN]; Alosetron hydrochloride (USAN); GR-68755C; Lotronex (TN); Lotrpnex (TN); 1H-Pyrido(4,3-b)indol-1-one, 2,3,4,5-tetrahydro-5-methyl-2((5-methyl-1H-imidazol-4-yl)methyl)-, monohydrochloride; 1H-Pyrido(4,3-b)indol-1-one, 2,3,4,5-tetrahydro-5-methyl-2-((5-methyl-1H-imidazol-4-yl)methyl)-, monohydrochloride; 1H-Pyrido[4,3-b]indol-1-one, 2,3,4,5-tetrahydro-5-methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]-, hydrochloride (1:1); 1H-Pyrido[4,3-b]indol-1-one, 2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl-1H-imidazol; 1H-Pyrido[4,3-b]indol-1-one, 2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-(9CI); 2,3,4,5-Tetrahydro-5-methyl-2-((5-methyl-1H-imidazol-4-yl)methyl)-1H-pyrido(4,3-b)indol-1-one; 2,3,4,5-Tetrahydro-5-methyl-2-((5-methylimidazol-4-yl)methyl)-1H-pyrido(4,3-b)indol-1-one monohydrochloride; 2,3,4,5-tetrahydro-5-methyl-2-((5-methylimidazol-4-yl)methyl)-1H-pyridol(4,3-b)indol-1-one monohydrochloride; 2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1H-pyrido[4,3-b]indol-1-one, monohydrochloride; 5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one; 5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one hydrochloride; 5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-3,4-dihydropyrido[4,3-b]indol-1-one; 5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-3,4-dihydropyrido[4,3-b]indol-1-one hydrochloride

Indication

Disease Entry	ICD 11	Status	REF
Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[1]
Irritable bowel syndrome	DD91.0	Approved	[2]
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Therapeutic Class

Gastrointestinal Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

294.35

Logarithm of the Partition Coefficient (xlogp)

1.6

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The absorption of drug is 50-60% []
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Bioavailability: 55% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The clearance of drug is 600 mL/min []
Elimination: 6% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 1.5 hours [5]
Metabolism: The drug is metabolized via the hepatic []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.10077 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.18% [5]
Vd: The volume of distribution (Vd) of drug is 65-95 L []
Water Solubility: The ability of drug to dissolve in water is measured as 61 mg/mL [3]

Chemical Identifiers

Formula: C17H18N4O
IUPAC Name: 5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-3,4-dihydropyrido[4,3-b]indol-1-one
Canonical SMILES: CC1=C(N=CN1)CN2CCC3=C(C2=O)C4=CC=CC=C4N3C
InChI: InChI=1S/C17H18N4O/c1-11-13(19-10-18-11)9-21-8-7-15-16(17(21)22)12-5-3-4-6-14(12)20(15)2/h3-6,10H,7-9H2,1-2H3,(H,18,19)
InChIKey: JSWZEAMFRNKZNL-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 2099
ChEBI ID: CHEBI:253342
CAS Number: 122852-42-0
DrugBank ID: DB00969
TTD ID: D06GKN
INTEDE ID: DR0073
ACDINA ID: D00023

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Antagonist	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Alosetron (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Increased metabolism of Alosetron caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[11]
Obeticholic acid	DM3Q1SM	Moderate	Decreased metabolism of Alosetron caused by Obeticholic acid mediated inhibition of CYP450 enzyme.	Autoimmune liver disease [DB96]	[12]
Clarithromycin	DM4M1SG	Moderate	Decreased metabolism of Alosetron caused by Clarithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Troleandomycin	DMUZNIG	Moderate	Decreased metabolism of Alosetron caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Telithromycin	DMZ4P3A	Moderate	Decreased metabolism of Alosetron caused by Telithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Alpelisib	DMEXMYK	Moderate	Increased metabolism of Alosetron caused by Alpelisib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[13]
Niclosamide	DMJAGXQ	Moderate	Decreased metabolism of Alosetron caused by Niclosamide mediated inhibition of CYP450 enzyme.	Cestodes infection [1F70-1F76]	[12]
Osilodrostat	DMIJC9X	Moderate	Decreased metabolism of Alosetron caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[12]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Alosetron caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[12]
Itraconazole	DMCR1MV	Moderate	Decreased metabolism of Alosetron caused by Itraconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[12]
Miconazole	DMPMYE8	Moderate	Decreased metabolism of Alosetron caused by Miconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[12]
Ketoconazole	DMPZI3Q	Moderate	Decreased metabolism of Alosetron caused by Ketoconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[12]
Fosamprenavir	DM4W9B3	Moderate	Decreased metabolism of Alosetron caused by Fosamprenavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Atazanavir	DMSYRBX	Moderate	Decreased metabolism of Alosetron caused by Atazanavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Teriflunomide	DMQ2FKJ	Moderate	Increased metabolism of Alosetron caused by Teriflunomide mediated induction of CYP450 enzyme.	Hyper-lipoproteinaemia [5C80]	[14]
Hydralazine	DMU8JGH	Minor	Decreased metabolism of Alosetron caused by Hydralazine mediated inhibition of non-CYP450 enzyme.	Hypertension [BA00-BA04]	[12]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Alosetron caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[12]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Alosetron caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[14]
Osimertinib	DMRJLAT	Moderate	Increased metabolism of Alosetron caused by Osimertinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[15]
Capmatinib	DMYCXKL	Moderate	Decreased metabolism of Alosetron caused by Capmatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[12]
Primaquine	DMWQ16I	Moderate	Decreased metabolism of Alosetron caused by Primaquine mediated inhibition of CYP450 enzyme.	Malaria [1F40-1F45]	[12]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Alosetron caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[12]
Exjade	DMHPRWG	Moderate	Decreased metabolism of Alosetron caused by Exjade mediated inhibition of CYP450 enzyme.	Mineral absorption/transport disorder [5C64]	[12]
Olaparib	DM8QB1D	Moderate	Increased metabolism of Alosetron caused by Olaparib mediated induction of CYP450 enzyme.	Ovarian cancer [2C73]	[14]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Alosetron caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[12]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Alosetron caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[16]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Alosetron caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[17]
LEE011	DMMX75K	Moderate	Decreased metabolism of Alosetron caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[18]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Alosetron caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[19]
Procainamide	DMNMXR8	Minor	Decreased metabolism of Alosetron caused by Procainamide mediated inhibition of non-CYP450 enzyme.	Ventricular tachyarrhythmia [BC71]	[12]
Propafenone	DMPIBJK	Moderate	Decreased metabolism of Alosetron caused by Propafenone mediated inhibition of CYP450 enzyme.	Ventricular tachyarrhythmia [BC71]	[12]
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⏷ Show the Full List of 31 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
FD&C blue no. 2	E00446	2723854	Colorant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
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⏷ Show the Full List of 7 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Alosetron 1 mg tablet	1 mg	Oral Tablet	Oral
Alosetron 0.5 mg tablet	0.5 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Alosetron FDA Label
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2296).
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7	Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43; quiz 1844.
8	Effect of alosetron on the pharmacokinetics of alprazolam. J Clin Pharmacol. 2001 Apr;41(4):452-4.
9	Effect of alosetron on the pharmacokinetics of fluoxetine. J Clin Pharmacol. 2001 Apr;41(4):455-8.
10	Optimizing outcomes with alosetron hydrochloride in severe diarrhea-predominant irritable bowel syndrome. Therap Adv Gastroenterol. 2010 May;3(3):165-72.
11	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
12	Product Information. Lotronex (alosetron). Glaxo Wellcome, Research Triangle Park, NC.
13	Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
14	Cerner Multum, Inc. "Australian Product Information.".
15	Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
16	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
17	Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
18	DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
19	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.