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Identification
Name Tamsulosin
Accession Number DB00706 (APRD00036)
Type small molecule
Groups approved
Description

Tamsulosin is a selective antagonist at alpha-1A and alpha-1B-adrenoceptors in the prostate, prostatic capsule, prostatic urethra, and bladder neck. At least three discrete alpha1-adrenoceptor subtypes have been identified: alpha-1A, alpha-1B and alpha-1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha1-receptors in human prostate are of the alpha-1A subtype. Blockage of these receptors causes relaxation of smooth muscles in the bladder neck and prostate.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • tamsulosin
  • YM-617
Brand names
  • Flomax
  • Harnal
  • Omnic
  • Pradif
  • Tamsolusin
  • Tamsulosina [INN-Spanish]
  • Tamsulosine [INN-French]
  • Tamsulosinum [INN-Latin]
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Adrenergic alpha-Antagonists
CAS number 106133-20-4
Weight Average: 408.512
Monoisotopic: 408.171892706
Chemical Formula C20H28N2O5S
InChI Key InChIKey=DRHKJLXJIQTDTD-OAHLLOKOSA-N
InChI
InChI=1S/C20H28N2O5S/c1-4-26-17-7-5-6-8-18(17)27-12-11-22-15(2)13-16-9-10-19(25-3)20(14-16)28(21,23)24/h5-10,14-15,22H,4,11-13H2,1-3H3,(H2,21,23,24)/t15-/m1/s1
Plain Text
IUPAC Name
5-[(2R)-2-{[2-(2-ethoxyphenoxy)ethyl]amino}propyl]-2-methoxybenzene-1-sulfonamide
SMILES
CCOC1=C(OCCN[C@H](C)CC2=CC(=C(OC)C=C2)S(N)(=O)=O)C=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzenesulfonamides
  • Phenethylamines
  • Amphetamines
Substructures
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Sulfonyls
  • Ethers
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Catechols
  • Phenethylamines
  • Aromatic compounds
  • Anisoles
  • Sulfonamides
  • Phenyl Esters
  • Amphetamines
Pharmacology
Indication Used in the treatment of signs and symptoms of benign prostatic hyperplasia (reduction in urinary obstruction and relief of associated manifestations such as hesitancy, terminal dribbling of urine, interrupted or weak stream...etc.)
Pharmacodynamics Tamsulosin, a sulfamoylphenethylamine-derivative alpha-adrenoceptor blocker with enhanced specificity for the alpha-adrenoceptors of the prostate, is commonly used to treat benign prostatic hyperplasia (BPH). The drug is commercially available in a racemic mixture of 2 isomers, and is pharmacologically related to doxazocin, prazosin, and terazosin. However, unlike these drugs, tamsulosin has a higher affinity for the alpha-1A- adrenergic receptors, which are located in vascular smooth muscle. Studies show that tamsulosin has about 12 times greater affinity for alpha-1 adrenergic receptors in the prostate than those in the aorta, which may result in a reduced incidence of adverse cardiovascular effects.
Mechanism of action Tamsulosin is a selective antagonist at alpha-1A and alpha-1B-adrenoceptors in the prostate, prostatic capsule, prostatic urethra, and bladder neck. At least three discrete alpha1-adrenoceptor subtypes have been identified: alpha-1A, alpha-1B and alpha-1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha1-receptors in human prostate are of the alpha-1A subtype. Blockage of these receptors causes relaxation of smooth muscles in the bladder neck and prostate, and thus decreases urinary outflow resistance in men.
Absorption Absorption of tamsulosin HCI from capsules 0.4 mg is essentially complete (>90%) following oral administration under fasting conditions.
Volume of distribution
  • 16 L [intravenous administration to ten healthy male adults]
Protein binding 94%-99%
Metabolism

Tamsulosin HCI is extensively metabolized by cytochrome P450 enzymes in the liver, however, the pharmacokinetic profile of the metabolites in humans has not been established.
Route of elimination Tamsulosin hydrochloride is extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged. The metabolites of tamsulosin hydrochloride undergo extensive conjugation to glucuronide or sulfate prior to renal excretion. On administration of the radiolabeled dose of tamsulosin hydrochloride to four healthy volunteers, 97% of the administered radioactivity was recovered, with urine (76%) representing the primary route of excretion compared to feces (21%) over 168 hours.
Half life 5-7 hours
Clearance
  • 2.88 L/h
Toxicity LD50 = 650 mg/kg (in rats)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Boehringer ingelheim pharmaceuticals inc
  • Impax laboratories inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Synthon pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Wockhardt ltd
  • Zydus pharmaceuticals usa inc
Packagers
Dosage forms
Form Route Strength
Capsule, extended release Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Flomax 0.4 mg capsule 4.71 USD capsule
Tamsulosin hcl 0.4 mg capsule 4.3 USD capsule
Flomax Cr 0.4 mg Extended-Release Tablet 0.63 USD tablet
Mylan-Tamsulosin 0.4 mg Sustained-Release Capsule 0.63 USD capsule
Novo-Tamsulosin 0.4 mg Sustained-Release Capsule 0.57 USD capsule
Ran-Tamsulosin 0.4 mg Sustained-Release Capsule 0.57 USD capsule
Ratio-Tamsulosin 0.4 mg Sustained-Release Capsule 0.57 USD capsule
Sandoz Tamsulosin 0.4 mg Sustained-Release Capsule 0.57 USD capsule
Tamsulosin 0.4 mg Sustained-Release Capsule 0.57 USD capsule
Patents
Country Patent Number Approved Expires
United States 4703063 1993-04-27 2010-04-27
Canada 2490299 2008-08-26 2023-12-24
Canada 2144077 2005-05-24 2013-09-10
Properties
State solid
Melting point 226-228 oC (HCl salt)
Experimental Properties
Property Value Source
water solubility Sparingly soluble in water PhysProp
logP 2.3 PhysProp
Predicted Properties
Property Value Source
water solubility 6.55e-03 g/l ALOGPS
logP 3.05 ALOGPS
logP 2.02 ChemAxon Molconvert
logS -4.79 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 99.88 ChemAxon Molconvert
rotatable bond count 11 ChemAxon Molconvert
refractivity 108.86 ChemAxon Molconvert
polarizability 43.95 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Dunn CJ, Matheson A, Faulds DM: Tamsulosin: a review of its pharmacology and therapeutic efficacy in the management of lower urinary tract symptoms. Drugs Aging. 2002;19(2):135-61. Pubmed
  2. Lyseng-Williamson KA, Jarvis B, Wagstaff AJ: Tamsulosin: an update of its role in the management of lower urinary tract symptoms. Drugs. 2002;62(1):135-67. Pubmed
  3. Wilt TJ, Mac Donald R, Rutks I: Tamsulosin for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2003;(1):CD002081. Pubmed
External Links
Resource Link
KEGG Compound C07124 Link_out
PubChem Compound 129211 Link_out
PubChem Substance 46507763 Link_out
ChemSpider 114457 Link_out
ChEBI 9398 Link_out
ChEMBL 9398 Link_out
Therapeutic Targets Database DAP000086 Link_out
Drug Product Database 2238123 Link_out
RxList http://www.rxlist.com/cgi/generic2/tamsul.htm Link_out
Drugs.com http://www.drugs.com/cdi/tamsulosin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Tamsulosin Link_out
ATC Codes
  • G04CA02
AHFS Codes
  • 92:00.00
PDB Entries Not Available
FDA label show (248.2 KB)
MSDS show (20.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take 30 minutes after a meal (always after the same meal). Taking the drug with food minimizes plasma levels variations.
Targets

1. Alpha-1A adrenergic receptor

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Abrams P, Speakman M, Stott M, Arkell D, Pocock R: A dose-ranging study of the efficacy and safety of tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist, in patients with benign prostatic obstruction (symptomatic benign prostatic hyperplasia). Br J Urol. 1997 Oct;80(4):587-96. Pubmed
  3. Na YJ, Guo YL, Gu FL: Clinical comparison of selective and non-selective alpha 1A-adrenoceptor antagonists for bladder outlet obstruction associated with benign prostatic hyperplasia: studies on tamsulosin and terazosin in Chinese patients. The Chinese Tamsulosin Study Group. J Med. 1998;29(5-6):289-304. Pubmed
  4. Lee E, Lee C: Clinical comparison of selective and non-selective alpha 1A-adrenoreceptor antagonists in benign prostatic hyperplasia: studies on tamsulosin in a fixed dose and terazosin in increasing doses. Br J Urol. 1997 Oct;80(4):606-11. Pubmed
  5. Chapple CR, Wyndaele JJ, Nordling J, Boeminghaus F, Ypma AF, Abrams P: Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. A meta-analysis of two randomized, placebo-controlled, multicentre studies in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin Study Group. Eur Urol. 1996;29(2):155-67. Pubmed
  6. Schulman CC, Cortvriend J, Jonas U, Lock TM, Vaage S, Speakman MJ: Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. Analysis of a multinational, multicentre, open-label study assessing the long-term efficacy and safety in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin Study Group. Eur Urol. 1996;29(2):145-54. Pubmed
  7. Chen Y, Li H, Dong Q, Wang KJ: Blockade of alpha 1A-adrenoceptor: a novel possible strategy for male contraception. Med Hypotheses. 2009 Aug;73(2):140-1. Epub 2009 May 8. Pubmed
  8. Michel MC, de la Rosette JJ: Efficacy and safety of tamsulosin in the treatment of urological diseases. Expert Opin Pharmacother. 2004 Jan;5(1):151-60. Pubmed

2. Alpha-1D adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

Organism class: human
UniProt ID: P25100 Link_out
Gene: ADRA1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Noble AJ, Chess-Williams R, Couldwell C, Furukawa K, Uchyiuma T, Korstanje C, Chapple CR: The effects of tamsulosin, a high affinity antagonist at functional alpha 1A- and alpha 1D-adrenoceptor subtypes. Br J Pharmacol. 1997 Jan;120(2):231-8. Pubmed
  3. Lowe FC: Summary of clinical experiences with tamsulosin for the treatment of benign prostatic hyperplasia. Rev Urol. 2005;7 Suppl 4:S13-21. Pubmed
  4. Tomiyama Y, Tatemichi S, Tadachi M, Kobayashi S, Hayashi M, Kobayashi M, Yamazaki Y, Shibata N: [Effect of silodosin on intraurethral pressure increase induced by hypogastric nerve stimulation in dogs with benign prostatic hyperplasia] Yakugaku Zasshi. 2006 Mar;126 Spec no.:225-30. Pubmed
  5. Ishiguro M, Futabayashi Y, Ohnuki T, Ahmed M, Muramatsu I, Nagatomo T: Identification of binding sites of prazosin, tamsulosin and KMD-3213 with alpha(1)-adrenergic receptor subtypes by molecular modeling. Life Sci. 2002 Oct 11;71(21):2531-41. Pubmed
  6. Taguchi K, Saitoh M, Sato S, Asano M, Michel MC: Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes. J Pharmacol Exp Ther. 1997 Jan;280(1):1-5. Pubmed
  7. Michel MC, de la Rosette JJ: Efficacy and safety of tamsulosin in the treatment of urological diseases. Expert Opin Pharmacother. 2004 Jan;5(1):151-60. Pubmed

3. Alpha-1B adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ishiguro M, Futabayashi Y, Ohnuki T, Ahmed M, Muramatsu I, Nagatomo T: Identification of binding sites of prazosin, tamsulosin and KMD-3213 with alpha(1)-adrenergic receptor subtypes by molecular modeling. Life Sci. 2002 Oct 11;71(21):2531-41. Pubmed
  2. Michel MC, Hanft G, Gross G: Functional studies on alpha 1-adrenoceptor subtypes mediating inotropic effects in rat right ventricle. Br J Pharmacol. 1994 Feb;111(2):539-46. Pubmed
  3. Taguchi K, Saitoh M, Sato S, Asano M, Michel MC: Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes. J Pharmacol Exp Ther. 1997 Jan;280(1):1-5. Pubmed
  4. Richardson CD, Donatucci CF, Page SO, Wilson KH, Schwinn DA: Pharmacology of tamsulosin: saturation-binding isotherms and competition analysis using cloned alpha 1-adrenergic receptor subtypes. Prostate. 1997 Sep 15;33(1):55-9. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  6. Michel MC, de la Rosette JJ: Efficacy and safety of tamsulosin in the treatment of urological diseases. Expert Opin Pharmacother. 2004 Jan;5(1):151-60. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Carriers

1. Alpha-1-acid glycoprotein 1

Appears to function in modulating the activity of the immune system during the acute-phase reaction

UniProt ID: P02763 Link_out
Gene: ORM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Matsushima H, Watanabe T, Higuchi S: Effect of alpha(1)-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil. J Pharm Sci. 2000 Apr;89(4):490-8. Pubmed
  2. Hanada K, Tochikura N, Ogata H: Selective binding of tamsulosin to genetic variants of human alpha1-acid glycoprotein. Biol Pharm Bull. 2007 Aug;30(8):1593-5. Pubmed
  3. Koiso K, Akaza H, Kikuchi K, Aoyagi K, Ohba S, Miyazaki M, Ito M, Sueyoshi T, Matsushima H, Kamimura H, Watanabe T, Higuchi S: Pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment: effects of alpha 1-acid glycoprotein. J Clin Pharmacol. 1996 Nov;36(11):1029-38. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.