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Identification
Name Terazosin
Accession Number DB01162 (APRD00667)
Type small molecule
Groups approved
Description

Terazosin is a selective alpha1-antagonist used for treatment of symptoms of benign prostatic hyperplasia (BPH). It also acts to lower blood pressure, so it is a drug of choice for men with hypertension and prostate enlargement. It works by blocking the action of adrenaline on smooth muscle of the bladder and the blood vessel walls.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Abbott 45975
  • Terazosin HCl
  • Terazosin hydrochloride
  • Terazosina [INN-Spanish]
  • Terazosine
  • Terazosine [INN-French]
  • Terazosinum [INN-Latin]
  • Trazosin HCl
Brand names
  • Blavin (Baliarda (Argentina))
  • Flumarc (Raffo (Argentina))
  • Fosfomic (Finadiet (Argentina))
  • Heitrin (Abbott (Germany; discontinued))
  • Hytracin
  • Hytrin (Abbott)
  • Hytrinex (Amdipharm (Sweden))
  • Itrin (Keryos (Italy))
  • Urodie (Keryos (Italy))
  • Vasomet
  • Vicard (Amdipharm (Austria))
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Adrenergic alpha-Antagonists
CAS number 63590-64-7
Weight Average: 387.4329
Monoisotopic: 387.190654313
Chemical Formula C19H25N5O4
InChI Key InChIKey=VCKUSRYTPJJLNI-UHFFFAOYSA-N
InChI
InChI=1S/C19H25N5O4/c1-26-15-10-12-13(11-16(15)27-2)21-19(22-17(12)20)24-7-5-23(6-8-24)18(25)14-4-3-9-28-14/h10-11,14H,3-9H2,1-2H3,(H2,20,21,22)
Plain Text
IUPAC Name
6,7-dimethoxy-2-{4-[(oxolan-2-yl)carbonyl]piperazin-1-yl}quinazolin-4-amine
SMILES
COC1=CC2=C(C=C1OC)C(N)=NC(=N2)N1CCN(CC1)C(=O)C1CCCO1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Quinazolines
Substructures
  • Quinazolines
  • Phenols and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Piperazines
  • Ethers
  • Benzene and Derivatives
  • Pyrimidines and Derivatives
  • Catechols
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Furans
  • Cyanamides
  • Phenyl Esters
Pharmacology
Indication For the treatment of symptomatic BPH and mild to moderate hypertension.
Pharmacodynamics Terazosin, classified as a quinazoline, is similar to doxazosin and prazosin. As an α-adrenergic blocking agent, terazosin is used to treat hypertension and BPH. Terazosin produces vasodilation and reduces peripheral resistance but in general has only a slight effect on cardiac output. The antihypertensive effect with chronic dosing is not usually accompanied by reflex tachycardia.
Mechanism of action In general, α1-adrenergic receptors mediate contraction and hypertrophic growth of smooth muscle cells. α1-Receptors are 7-transmembrane domain receptors coupled to G proteins, Gq/11. Three α1-receptor subtypes, which share approximately 75% homology in their transmembrane domains, have been identified: α1A (chromosome 8), α1B (chromosome 5), and α1D (chromosome 20). Terazosin is the first α1-receptor antagonist to demonstrate selectivity for the α1A-receptor. All three receptor subtypes appear to be involved in maintaining vascular tone. The α1A-receptor maintains basal vascular tone while the α1B-receptor mediates the vasocontrictory effects of exogenous α1-agonists. Activation of α1-receptors activates Gq-proteins, which results in intracellular stimulation of phospholipases C, A2, and D. This results in mobilization of Ca2+ from intracellular stores, activation of mitogen-activated kinase and PI3 kinase pathways and subsequent vasoconstriction. Terozosin produces its pharmacological effects by inhibiting α1A-receptor activation. Inhibition of these receptors in the vasculature and prostate results in muscle relaxation, decreased blood pressure and improved urinary outflow in symptomatic benign prostatic hyperplasia.
Absorption Essentially completely absorbed in man (90% bioavailability).
Volume of distribution Not Available
Protein binding 90-94%
Metabolism

Hepatic. One of the four metabolites identified (piperazine derivative of terazosin) has antihypertensive activity.
Route of elimination Approximately 10% of an orally administered dose is excreted as parent drug in the urine and approximately 20% is excreted in the feces.
Half life 12 hours
Clearance Not Available
Toxicity LD50=259.3mg/kg (IV in mice)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Apotex inc
  • Cadista pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan laboratories inc
  • Mylan technologies inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Teva pharmaceuticals usa inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral 1 mg
Capsule Oral 10 mg
Capsule Oral 2 mg
Capsule Oral 5 mg
Tablet Oral 1 mg
Tablet Oral 10 mg
Tablet Oral 2 mg
Tablet Oral 5 mg
Prices
Unit description Cost Unit
Hytrin 10 mg Tablet 1.85 USD tablet
Terazosin HCl 1 mg capsule 1.67 USD capsule
Terazosin HCl 10 mg capsule 1.67 USD capsule
Terazosin HCl 2 mg capsule 1.67 USD capsule
Terazosin HCl 5 mg capsule 1.67 USD capsule
Hytrin 5 mg Tablet 1.26 USD tablet
Hytrin 2 mg Tablet 0.93 USD tablet
Apo-Terazosin 10 mg Tablet 0.92 USD tablet
Novo-Terazosin 10 mg Tablet 0.92 USD tablet
Nu-Terazosin 10 mg Tablet 0.92 USD tablet
Pms-Terazosin 10 mg Tablet 0.92 USD tablet
Ratio-Terazosin 10 mg Tablet 0.92 USD tablet
Hytrin 1 mg Tablet 0.73 USD tablet
Apo-Terazosin 5 mg Tablet 0.63 USD tablet
Novo-Terazosin 5 mg Tablet 0.63 USD tablet
Nu-Terazosin 5 mg Tablet 0.63 USD tablet
Pms-Terazosin 5 mg Tablet 0.63 USD tablet
Ratio-Terazosin 5 mg Tablet 0.63 USD tablet
Apo-Terazosin 2 mg Tablet 0.46 USD tablet
Novo-Terazosin 2 mg Tablet 0.46 USD tablet
Nu-Terazosin 2 mg Tablet 0.46 USD tablet
Pms-Terazosin 2 mg Tablet 0.46 USD tablet
Ratio-Terazosin 2 mg Tablet 0.46 USD tablet
Apo-Terazosin 1 mg Tablet 0.37 USD tablet
Novo-Terazosin 1 mg Tablet 0.37 USD tablet
Nu-Terazosin 1 mg Tablet 0.37 USD tablet
Pms-Terazosin 1 mg Tablet 0.37 USD tablet
Ratio-Terazosin 1 mg Tablet 0.37 USD tablet
Patents
Country Patent Number Approved Expires
United States 5294615 1993-04-29 2013-04-29
United States 5212176 1993-06-29 2010-06-29
Properties
State solid
Melting point 273 oC
Experimental Properties
Property Value Source
water solubility 29.7mg/mL PhysProp
logP 1 PhysProp
Predicted Properties
Property Value Source
water solubility 1.50e+00 g/l ALOGPS
logP 1.12 ALOGPS
logP 1.18 ChemAxon Molconvert
logS -2.41 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 8 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 103.04 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 105.18 ChemAxon Molconvert
polarizability 41.26 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM: Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404. Pubmed
External Links
Resource Link
KEGG Compound C07127 Link_out
PubChem Compound 5401 Link_out
PubChem Substance 46509129 Link_out
ChemSpider 5208 Link_out
ChEBI 9445 Link_out
ChEMBL 9445 Link_out
Therapeutic Targets Database DAP000371 Link_out
PharmGKB PA451612 Link_out
Drug Product Database 2243749 Link_out
RxList http://www.rxlist.com/cgi/generic/teraz.htm Link_out
Drugs.com http://www.drugs.com/terazosin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Terazosin Link_out
ATC Codes
  • G04CA03
AHFS Codes
  • 24:20.00
PDB Entries Not Available
FDA label show (1020.4 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
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. Chapple CR: Medical therapy and quality of life. Eur Urol. 1998;34 Suppl 2:10-7; discussion 46. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. 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
  4. Michel MC, Grubbel B, Taguchi K, Verfurth F, Otto T, Kropfl D: Drugs for treatment of benign prostatic hyperplasia: affinity comparison at cloned alpha 1-adrenoceptor subtypes and in human prostate. J Auton Pharmacol. 1996 Feb;16(1):21-8. Pubmed
  5. 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
  6. Roehrborn CG, Schwinn DA: Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol. 2004 Mar;171(3):1029-35. Pubmed

2. Alpha-1B 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

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

References:
  1. Boyle P, Robertson C, Manski R, Padley RJ, Roehrborn CG: Meta-analysis of randomized trials of terazosin in the treatment of benign prostatic hyperplasia. Urology. 2001 Nov;58(5):717-22. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Simpson P: Stimulation of hypertrophy of cultured neonatal rat heart cells through an alpha 1-adrenergic receptor and induction of beating through an alpha 1- and beta 1-adrenergic receptor interaction. Evidence for independent regulation of growth and beating. Circ Res. 1985 Jun;56(6):884-94. Pubmed
  4. Vincent J, Dachman W, Blaschke TF, Hoffman BB: Pharmacological tolerance to alpha 1-adrenergic receptor antagonism mediated by terazosin in humans. J Clin Invest. 1992 Nov;90(5):1763-8. Pubmed

3. Alpha-1D adrenergic receptor

Pharmacological action: yes
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

4. Potassium voltage-gated channel subfamily H member 2

Pharmacological action: unknown
Actions: inhibitor

Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1

Organism class: human
UniProt ID: Q12809 Link_out
Gene: KCNH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. Pubmed

5. Potassium voltage-gated channel subfamily H member 6

Pharmacological action: unknown
Actions: inhibitor

Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current. Channel properties may be modulated by cAMP and subunit assembly

Organism class: human
UniProt ID: Q9H252 Link_out
Gene: KCNH6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. Pubmed

6. Potassium voltage-gated channel subfamily H member 7

Pharmacological action: unknown
Actions: inhibitor

Pore-forming (alpha) subunit of voltage-gated potassium channel. Channel properties may be modulated by cAMP and subunit assembly

Organism class: human
UniProt ID: Q9NS40 Link_out
Gene: KCNH7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Takara K, Sakaeda T, Kakumoto M, Tanigawara Y, Kobayashi H, Okumura K, Ohnishi N, Yokoyama T: Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport. Oncol Res. 2009;17(11-12):527-33. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:08

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.