Sennosides
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Overview
- Description
- A medication used to treat constipation.
- Description
- A medication used to treat constipation.
- DrugBank ID
- DB11365
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 0
- Phase 2
- 4
- Phase 3
- 4
- Phase 4
- 8
- Mechanism of Action
- Aquaporin-3Inhibitor
- Aquaporin-3
Identification
- Summary
Sennosides is a laxative used to treat constipation.
- Brand Names
- Colace, EX-lax Chocolated, EX-lax Maximum Relief Formula, EX-lax Regular Strength Pills, Laxacin, Little Tummys Laxative Drops, Perdiem Overnight, Peri-colace Reformulated Feb 2008, Senexon, Senexon S, Senna Lax, Senna-time, Senokot, Senokot-S
- Generic Name
- Sennosides
- DrugBank Accession Number
- DB11365
- Background
Sennosides (also known as senna glycoside or senna) is a medication used to treat constipationLabel12 and empty the large intestine before surgery. The medication is taken by mouth or via the rectumLabel. It typically begins working in minutes when given by rectum and within twelve hours when given by mouthLabel. It is a weaker laxative than bisacodyl or castor oil11. Sennoside A, one of the sennosides present in the laxative medication, has recently proven effective in inhibiting the ribonuclease H (RNase H) activity of human immunodeficiency virus (HIV) reverse transcriptase 1.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 862.746
Monoisotopic: 862.195643624 - Chemical Formula
- C42H38O20
- Synonyms
- Senna glycosides
- Sennoside
- Sennosides
Pharmacology
- Indication
For the over the counter treatment of constipationLabel12.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination for symptomatic treatment of Constipation Combination Product in combination with: Plantago ovata seed (DB14585), Plantago seed (DB11097) ••• ••• •••••••• ••• •••••••• Used in combination to manage Constipation Combination Product in combination with: Plantago seed (DB11097) •••••••••••• ••••••• Used in combination to treat Constipation Combination Product in combination with: Bisacodyl (DB09020) •••••••••••• ••••••• •••• •••••• Used in combination to treat Constipation Combination Product in combination with: Octasulfur (DB09353), Activated charcoal (DB09278), Rhubarb (DB10651) •••••••••••• •••••• Symptomatic treatment of Constipation ••• ••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Senna stimulates peristalsis and increases fecal water content to increase motility of feces through the large intestine6,2,12.
- Mechanism of action
Sennoside A and B, the components of senna, are metabolized by gut bacteria into the active metabolite rheinanthrone Rheinanthrone2. Rheinanthrone Rheinanthrone appears to increase cyclooxegenase 2 (COX2) expression in macrophage cells leading to an increase in prostaglandin E2 (PGE2)2. This increase in PGE2 is associated with a decrease in aquaporin 3 expression in mucosal epithelial cells of the large intestine2. A decrease in aquaporin 3 expression likely produces the laxative effect by restricting water reabsorption by the large intestine thereby increasing fecal water content2. The exact mechanism by which rheinanthrone increases COX2 expression is unknown2. Rheinanthrone Rheinanthrone also stimulates peristalsis in the large intestine although the mechanism behind this effect is unknown6. Rhein Rhein, another active metabolite is thought to excite submucosal acetylcholinergic neurons resulting in increased chloride and prostaglandin secretion8,9. The movement of chloride ions into the large intestine would also help to draw water into the lumen9.
Target Actions Organism AAquaporin-3 inhibitorHumans UReverse transcriptase/RNaseH inhibitorHuman immunodeficiency virus 1 - Absorption
<10% is absorbed from the gut mostly in the form of the active metabolite rheinanthrone [Rheinanthrone](https://go.drugbank.com/drugs/DB13175)12.
- Volume of distribution
The volume of distribution of radiolabelled intravenous sennoside B in rats was 0.802±0.124L/kg10.
- Protein binding
Because sennosides are ingested and their action occurs in the gut, it is generally not thought to be protein bound2.
- Metabolism
Sennosides A and B are metabolised to sennidins A and B by gut bacteria6. Sennidins A and B are further metabolized to rheinanthrone Rheinanthrone by gut bacteria using beta-glucosidase2. Rheinanthrone Rheinanthrone is absorbed into systemic circulation where 2.6% is metabolized to rhein Rhein and sennidins A and B via oxidation4,7,2. Rheinanthrone Rheinanthrone is the major active metabolite of sennosides A and B which produces the laxative effect of the medication2. Rhein Rhein is also an active metabolite known to have many protective effects8.
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- Route of elimination
3-6% of metabolites are excreted in urine with some in bile. >90% of sennosides are excreted in the feces as polymers with 2-6% of the parent compounds excreted unchanged12.
- Half-life
The half life of radiolabelled intravenous sennoside B in rats was 8.568±0.651h10.
- Clearance
The clearance of radiolabelled intravenous sennoside B in rats was 0.065±0.007L/h/kg10.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Senna causes increased amounts of apoptosis in the large intestine shortly after use due to upregulated p53 activity3. This is normally reversed after 18 hours however chronic use has been shown to be associated with p53 resistance and potential carcinogenicity leading to colon cancer3. The LD50 value in rats was 5000mg/kg. Subacute studies in rats receiving 20mg/kg and dogs receiving 500mg/kg did not produce signs of toxicity5. Tests for mutagenicity and reproductive toxicity do not indicate toxic effects5.
Sennosides are not recommended for use in pregnancy due to genotoxic risks associated with chemically similar compounds12. The active metabolite of sennosides is excreted in breast milk, though there are no reports of the laxitive effect in breast fed babies12. There is no data on the effects of sennosides on fertility12.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetazolamide The risk or severity of dehydration can be increased when Acetazolamide is combined with Sennosides. Aclidinium The therapeutic efficacy of Sennosides can be decreased when used in combination with Aclidinium. Alfentanil The therapeutic efficacy of Sennosides can be decreased when used in combination with Alfentanil. Alloin The risk or severity of adverse effects can be increased when Sennosides is combined with Alloin. Amantadine The therapeutic efficacy of Sennosides can be decreased when used in combination with Amantadine. - Food Interactions
- Avoid natural licorice. Licorice root can induce hypokalemia in patients taking sennosides.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Sennosides A and B 1B5FPI42EN 62211-03-4 Not applicable - Product Images
- Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Agarol Extra Strength Chewable Laxative Tablets Tablet 25 mg Oral Numark Laboratories, Inc. 2000-08-21 2009-07-31 Canada Agarol With Sennosides Liquid 25 mg / 15 mL Oral Numark Laboratories, Inc. 1999-06-30 2009-07-31 Canada Agoral Liquid 8.3 mg/5mL Oral Numark Brands, Inc 1942-05-05 2016-10-18 US Assured Natural Laxative Tablet, coated 8.6 mg/1 Oral Spirit Pharmaceuticals LLC 2016-08-12 2016-07-28 US BEKUNIS HERBAL TABLET 20 mg Tablet, coated 20 mg Oral PHARMAFORTE SINGAPORE PTE LTD 1991-04-03 Not applicable Singapore - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image 2 In 1laxative Stool Softener and Stiulant Laxative Sennosides (8.6 mg/1) + Docusate sodium (50 mg/1) Tablet, coated Oral Rite Aid Corporation 2020-06-01 Not applicable US 2 In 1laxative Stool Softener and Stiulant Laxative Sennosides (8.6 mg/1) + Docusate sodium (50 mg/1) Tablet, coated Oral Rite Aid Corporation 2020-06-01 Not applicable US AGIOLAX Sennosides (0.3 g) + Plantago seed (54.2 G) Granule Oral Viatris Healthcare Limited 2014-07-08 Not applicable Italy AGIOLAX Sennosides (0.3 g/100g) + Plantago seed (54.2 g/100g) Granule Oral Viatris Healthcare Limited 2014-07-08 Not applicable Italy AGIOLAX Sennosides (1.2 g) + Plantago seed (216.8 G) Granule Oral Viatris Healthcare Limited 2014-07-08 Not applicable Italy - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Medi-laxx Rx Stool Softener and Laxative Sennosides (8.6 mg/1) + Docusate sodium (50 mg/1) Tablet Oral Two Hip Consulting, Llc 2014-12-05 2016-04-11 US Senna Gen Sennosides (8.6 mg/1) Tablet Oral Cardinal Health 2011-06-07 2011-06-30 US Senna Plus Sennosides A and B (8.6 mg/1) + Docusate sodium (50 mg/1) Tablet, film coated Oral Major Pharmaceuticals 2010-01-14 2020-08-31 US Senna Plus Sennosides (8.6 mg/1) + Docusate sodium (50 ug/1) Tablet Oral Amerincan Health Packaging 2004-10-28 2014-08-31 US Senna Plus Sennosides A and B (8.6 mg/1) + Docusate sodium (50 mg/1) Tablet, film coated Oral Cardinal Health 2010-01-14 Not applicable US
Categories
- ATC Codes
- A06AB56 — Senna glycosides, combinations
- A06AB — Contact laxatives
- A06A — DRUGS FOR CONSTIPATION
- A06 — DRUGS FOR CONSTIPATION
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 3FYP5M0IJX
- CAS number
- 517-43-1
- InChI Key
- IPQVTOJGNYVQEO-UHFFFAOYSA-N
- InChI
- InChI=1S/C42H38O20/c43-11-23-31(47)35(51)37(53)41(61-23)59-21-5-1-3-15-25(17-7-13(39(55)56)9-19(45)27(17)33(49)29(15)21)26-16-4-2-6-22(60-42-38(54)36(52)32(48)24(12-44)62-42)30(16)34(50)28-18(26)8-14(40(57)58)10-20(28)46/h1-10,23-26,31-32,35-38,41-48,51-54H,11-12H2,(H,55,56)(H,57,58)
- IUPAC Name
- 4,4'-dihydroxy-10,10'-dioxo-5,5'-bis({[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy})-9H,9'H,10H,10'H-[9,9'-bianthracene]-2,2'-dicarboxylic acid
- SMILES
- OCC1OC(OC2=C3C(=O)C4=C(C=C(C=C4O)C(O)=O)C(C4C5=CC=CC(OC6OC(CO)C(O)C(O)C6O)=C5C(=O)C5=C4C=C(C=C5O)C(O)=O)C3=CC=C2)C(O)C(O)C1O
References
- General References
- Esposito F, Carli I, Del Vecchio C, Xu L, Corona A, Grandi N, Piano D, Maccioni E, Distinto S, Parolin C, Tramontano E: Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication. Phytomedicine. 2016 Nov 15;23(12):1383-1391. doi: 10.1016/j.phymed.2016.08.001. Epub 2016 Aug 10. [Article]
- Kon R, Ikarashi N, Nagoya C, Takayama T, Kusunoki Y, Ishii M, Ueda H, Ochiai W, Machida Y, Sugita K, Sugiyama K: Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract. J Ethnopharmacol. 2014 Feb 27;152(1):190-200. doi: 10.1016/j.jep.2013.12.055. Epub 2014 Jan 8. [Article]
- van Gorkom BA, Karrenbeld A, van der Sluis T, Zwart N, de Vries EG, Kleibeuker JH: Apoptosis induction by sennoside laxatives in man; escape from a protective mechanism during chronic sennoside use? J Pathol. 2001 Aug;194(4):493-9. [Article]
- Dreessen M, Eyssen H, Lemli J: The metabolism of sennosides A and B by the intestinal microflora: in vitro and in vivo studies on the rat and the mouse. J Pharm Pharmacol. 1981 Oct;33(10):679-81. [Article]
- Mengs U: Toxic effects of sennosides in laboratory animals and in vitro. Pharmacology. 1988;36 Suppl 1:180-7. [Article]
- Hardcastle JD, Wilkins JL: The action of sennosides and related compounds on human colon and rectum. Gut. 1970 Dec;11(12):1038-42. [Article]
- de Witte P, Lemli J: Metabolism of 14C-rhein and 14C-rhein anthrone in rats. Pharmacology. 1988;36 Suppl 1:152-7. [Article]
- Zhou YX, Xia W, Yue W, Peng C, Rahman K, Zhang H: Rhein: A Review of Pharmacological Activities. Evid Based Complement Alternat Med. 2015;2015:578107. doi: 10.1155/2015/578107. Epub 2015 Jun 22. [Article]
- Frieling T, Rupprecht C, Schemann M: Rhein stimulates electrogenic chloride secretion by activation of submucosal neurons in guinea pig colon. Pharmacology. 1993 Oct;47 Suppl 1:70-6. [Article]
- Zhang D, Huang D, Ji Y, Jiang C, Li Y, Gao M, Yao N, Liu X, Shao H, Jing S, Ni Y, Yin Z, Zhang J: Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent. J Drug Target. 2015 Feb;23(2):180-90. doi: 10.3109/1061186X.2014.971328. Epub 2014 Oct 20. [Article]
- Portalatin M, Winstead N: Medical management of constipation. Clin Colon Rectal Surg. 2012 Mar;25(1):12-9. doi: 10.1055/s-0032-1301754. [Article]
- Senokot Tablet Product Information [Link]
- External Links
- Human Metabolome Database
- HMDB34317
- KEGG Compound
- C10404
- PubChem Substance
- 347911200
- ChemSpider
- 5010
- BindingDB
- 92481
- 36387
- ChEBI
- 9112
- ChEMBL
- CHEMBL54481
- Wikipedia
- Senna_glycoside
- FDA label
- Download (335 KB)
- MSDS
- Download (34.9 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Other Colonoscopy Preparation Outcome 1 somestatus stop reason just information to hide Not Available Completed Prevention Constipation / Palliatives Treatments 1 somestatus stop reason just information to hide Not Available Terminated Treatment Chronic idiopathic constipation (CIC) 1 somestatus stop reason just information to hide Not Available Unknown Status Prevention Colostomy / Elective Surgeries / Hirschsprung Disease - Pull Through / Inflammatory Bowel Diseases (IBD) / Intestinal Obstruction / Meconium Ileus / Necrotizing Enterocolitis (NEC) 1 somestatus stop reason just information to hide 4 Completed Not Available Colonoscopy Preparation 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 25 mg Liquid Oral 25 mg / 15 mL Granule Oral Liquid Oral 8.3 mg/5mL Powder, for suspension Oral Solution Oral 200.000 mg Tablet, coated Oral 20 mg Tablet, coated Oral 185 mg Extract Oral 23 mg/1g Powder Oral 20 mg/0.5g Tablet, sugar coated Oral 20 mg/1 Tablet Oral 19.110 mg Powder 50 kg/50kg Powder 15 kg/15kg Tablet Oral 8.600 mg Liquid Oral .7 mg / mL Tablet, chewable Oral 8.6 mg/1 Bar, chewable Oral 15 mg/1 Tablet, chewable Oral 15 mg/1 Kit Oral Liquid Oral 25 mg/15mL Pill Oral 15 mg/1 Tablet, chewable Oral Granule, effervescent Oral Granule, for solution Oral Tablet Oral 17.200 mg Liquid Oral Tablet Oral 8.6 mg / tab Tablet Oral 12 mg Extract Oral 1000 mg/1g Powder Oral 1000 mg/1g Capsule Oral Tablet Oral 12 mg/1 Tablet, chewable Oral 3 mg/1 Tablet, sugar coated Oral 25 mg/1 Tablet Oral 1700000 mg Tablet Oral 17 mg Capsule, liquid filled Oral Tablet, film coated Oral 25 mg/1 Pill Oral 25 mg/1 Tablet Oral 15 mg Tablet, coated Oral 15 mg/1 Tablet, sugar coated Oral 15 mg/1 Solution Oral 1.5 mg/mL Solution Oral Tablet Oral 25 mg/1 Tablet Oral Liquid Oral 8.8 mg/1mL Tablet, coated Oral 25 mg/1 Tablet Oral 8.6 mg Tablet Oral 15 mg/1 Capsule Oral 15 mg Tablet, coated Oral 12 MG Granule 20 mg/5ml Liquid Oral 10.5 mg / pck Tablet, coated Oral Capsule Oral 8.6 mg/1 Capsule, gelatin coated Oral 8.6 mg/1 Capsule, liquid filled Oral 8.6 mg/1 Liquid Oral 415.36 mg/236mL Syrup Oral 417.12 mg/237mL Tablet, coated Oral 8.6 mg/1 Extract Oral 0.4 g Tablet Oral 8.6 mg/1 Liquid Oral 8.8 mg/5mL Tablet Oral Tablet, film coated Oral 8.6 mg/1 Tablet, film coated Oral Tablet, delayed release 20 mg Syrup Oral 8.8 mg/5mL Capsule, liquid filled Oral 17.2 mg/17.21 Capsule, liquid filled Oral 17.2 mg/1 Tablet, film coated Oral 17.2 mg/1 Tablet Oral 374 mg Pill Oral Tablet Oral 17.2 mg/1 Jelly Oral 5 mg / 7 g Tablet Oral 8.60 mg Capsule, gelatin coated Oral Capsule Oral 8.3 mg/1 Syrup Oral Granule, for solution Oral Tablet, coated Oral Powder, for solution Oral Powder, for solution Oral 0.15 g Liquid Oral 1.7 mg / mL Tablet Oral 20 mg Solution Oral 7.5 mg/5mL Tablet Oral 7.5 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.753 mg/mL ALOGPS logP 0.94 ALOGPS logP 1.19 Chemaxon logS -3.1 ALOGPS pKa (Strongest Acidic) 3.23 Chemaxon pKa (Strongest Basic) -4 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 20 Chemaxon Hydrogen Donor Count 12 Chemaxon Polar Surface Area 347.96 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 205.44 m3·mol-1 Chemaxon Polarizability 81.49 Å3 Chemaxon Number of Rings 8 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 263.5394 predictedDeepCCS 1.0 (2019) [M+H]+ 265.51868 predictedDeepCCS 1.0 (2019) [M+Na]+ 271.8408 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Water channel required to promote glycerol permeability and water transport across cell membranes (PubMed:12239222, PubMed:30420639). Acts as a glycerol transporter in skin and plays an important role in regulating SC (stratum corneum) and epidermal glycerol content. Involved in skin hydration, wound healing, and tumorigenesis. Provides kidney medullary collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Slightly permeable to urea and may function as a water and urea exit mechanism in antidiuresis in collecting duct cells. It may play an important role in gastrointestinal tract water transport and in glycerol metabolism (By similarity)
- Specific Function
- glycerol channel activity
- Gene Name
- AQP3
- Uniprot ID
- Q92482
- Uniprot Name
- Aquaporin-3
- Molecular Weight
- 31543.605 Da
References
- Kon R, Ikarashi N, Nagoya C, Takayama T, Kusunoki Y, Ishii M, Ueda H, Ochiai W, Machida Y, Sugita K, Sugiyama K: Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract. J Ethnopharmacol. 2014 Feb 27;152(1):190-200. doi: 10.1016/j.jep.2013.12.055. Epub 2014 Jan 8. [Article]
- Kind
- Protein
- Organism
- Human immunodeficiency virus 1
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- aspartic-type endopeptidase activity
- Gene Name
- pol
- Uniprot ID
- Q72547
- Uniprot Name
- Reverse transcriptase/RNaseH
- Molecular Weight
- 65223.615 Da
References
- Esposito F, Carli I, Del Vecchio C, Xu L, Corona A, Grandi N, Piano D, Maccioni E, Distinto S, Parolin C, Tramontano E: Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication. Phytomedicine. 2016 Nov 15;23(12):1383-1391. doi: 10.1016/j.phymed.2016.08.001. Epub 2016 Aug 10. [Article]
Drug created at February 10, 2016 16:40 / Updated at November 06, 2024 16:18