TERAZOSIN HYDROCHLORIDE ANHYDROUS

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H25N5O4.ClH
Molecular Weight	423.894
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of TERAZOSIN HYDROCHLORIDE ANHYDROUS

Structure Search

SMILES

Cl.COC1=CC2=NC(=NC(N)=C2C=C1OC)N3CCN(CC3)C(=O)C4CCCO4

InChI

InChIKey=IWSWDOUXSCRCKW-UHFFFAOYSA-N

InChI=1S/C19H25N5O4.ClH/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);1H

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/75140_Terazosin%20Hydrochloride_prntlbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10503165

Terazosin (marketed as Hytrin or Zayasel) 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. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2462301	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/75140_Terazosin%20Hydrochloride_prntlbl.pdf	Curative		Approved 8429	TERAZOSIN HYDROCHLORIDE Approved Use are used to treat high blood preassure (hypertension); are also used to treat benign prostatic hyperplasia (BPH) in men Launch Date 2000
Benign prostatic hyperplasia 28 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/75140_Terazosin%20Hydrochloride_prntlbl.pdf	Primary		Approved 8429	TERAZOSIN HYDROCHLORIDE Approved Use are used to treat high blood preassure (hypertension); are also used to treat benign prostatic hyperplasia (BPH) in men Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
48 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1685091	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TERAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
37 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1685091	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TERAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
408 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1685091	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TERAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
418 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1685091	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TERAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1685091	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TERAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
9.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1685091	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		TERAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
8% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2872802			TERAZOSIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11028256 Page: p.1169	unhealthy n = 14 Health Status: unhealthy Condition: Hypertension Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/11028256 Page: p.1169	Disc. AE: Dizziness... AEs leading to discontinuation/dose reduction: Dizziness Sources: https://pubmed.ncbi.nlm.nih.gov/11028256 Page: p.1169
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1678920 Page: p.903	unhealthy n = 37 Health Status: unhealthy Condition: Hypertension Population Size: 37 Sources: https://pubmed.ncbi.nlm.nih.gov/1678920 Page: p.903	Disc. AE: Syncope... AEs leading to discontinuation/dose reduction: Syncope (2.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/1678920 Page: p.903
20 mg 1 times / day multiple, oral MTD Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.9	unhealthy Health Status: unhealthy Condition: Benign Prostatic Hyperplasia\|Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.9	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.9
10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.6	unhealthy Health Status: unhealthy Condition: Benign Prostatic Hyperplasia\|Hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.6	Other AEs: Syncope, Postural hypotension... Other AEs: Syncope Postural hypotension Priapism Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.6
20 mg 1 times / day multiple, oral (max) Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7533452 Page: p.409	unhealthy n = 494 Health Status: unhealthy Condition: Benign Prostatic Hyperplasia Sex: M Population Size: 494 Sources: https://pubmed.ncbi.nlm.nih.gov/7533452 Page: p.409	Disc. AE: Dizziness, Asthenia... AEs leading to discontinuation/dose reduction: Dizziness (6.7%) Asthenia (3.8%) Somnolence (2%) Chest pain (1.6%) Headache (1.2%) Dyspnea (1.2%) Prostate carcinoma (1%) Sources: https://pubmed.ncbi.nlm.nih.gov/7533452 Page: p.409
20 mg 1 times / day multiple, oral (max) Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.12	unhealthy n = 636 Health Status: unhealthy Condition: Benign Prostatic Hyperplasia Sex: M Population Size: 636 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.12	Disc. AE: Fever, Headache... AEs leading to discontinuation/dose reduction: Fever (0.5%) Headache (1.1%) Postural hypotension (0.5%) Syncope (0.5%) Nausea (0.5%) Dizziness (2%) Vertigo (0.5%) Dyspnea (0.5%) Blurred vision (0.6%) Amblyopia (0.6%) Urinary tract infection (0.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.12
40 mg 1 times / day multiple, oral (max) Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.16	unhealthy n = 859 Health Status: unhealthy Condition: Hypertension Population Size: 859 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.16	Disc. AE: Asthenia, Headache... AEs leading to discontinuation/dose reduction: Asthenia (1.6%) Headache (1.3%) Palpitations (1.4%) Postural hypotension (0.5%) Syncope (0.5%) Tachycardia (0.6%) Nausea (0.8%) Peripheral edema (0.6%) Dizziness (3.1%) Paresthesia (0.8%) Somnolence (0.6%) Dyspnea (0.9%) Nasal congestion (0.6%) Blurred vision (0.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19057Orig1s021,%2020347Orig1s009%20lbl.pdf Page: p.16

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP2 383	CYP 270

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22077101/	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0099542808605444	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/15098086/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9445	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9445
ChemicalBook	CB22630517	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB22630517
ChemicalBook	CB2285511	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2285511
ChemicalBook	CB73360180	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB73360180
ChemicalBook	CB9285510	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9285510
MolPort	MolPort-001-684-489	https://www.molport.com/shop/molecule-link/MolPort-001-684-489
eMolecules	902550	https://www.emolecules.com/cgi-bin/more?vid=902550

PubMed

Title	Date	PubMed
Alpha 1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia.	1999 Jun	10332490
Use of terazosine in patients with chronic pelvic pain syndrome and evaluation by prostatitis symptom score index.	2001	11583367
Lower urinary tract symptoms suggestive of benign prostatic obstruction--Triumph: the role of general practice databases.	2001	11275742
5alpha-reductase inhibitors: what role should they play?	2001 Dec	11750255
Initiation of nonselective alpha1-antagonist therapy and occurrence of hypotension-related adverse events among men with benign prostatic hyperplasia: a retrospective cohort study.	2001 May	11394731
Terazosin for benign prostatic hyperplasia.	2002	12519611
The use of alpha-adrenoceptor antagonists in lower urinary tract disease.	2002 Feb	11829730
Urodynamic effects of terazosin treatment for Japanese patients with symptomatic benign prostatic hyperplasia.	2002 Jun	11992065
Alpha1-adrenoceptor antagonists radiosensitize prostate cancer cells via apoptosis induction.	2002 May-Jun	12168853
Mice expressing the alpha(1B)-adrenergic receptor induces a synucleinopathy with excessive tyrosine nitration but decreased phosphorylation.	2002 Nov	12390524
Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).	2002 Nov-Dec	12461301
Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effects.	2002 Oct	12356082
[alpha 1-receptor blockade in therapy of benign prostatic hyperplasia syndrome. Correct dosing for optimal effectiveness].	2002 Sep	12426862
Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance.	2003 Apr	12629407
The role of combination therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia.	2003 Aug	12882718
Immobility from administration of the alpha1-adrenergic antagonist, terazosin, in the IVth ventricle in rats.	2003 Dec 26	14665423
Nitric oxide opposes glucose-induced hypertension by suppressing sympathetic activity.	2003 Feb	12574094
Terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome: a randomized, placebo controlled trial.	2003 Feb	12544314
[Results of treatment of irritative symptoms and urinary retention in patients 1 year after radical retropubic prostatectomy].	2003 Jan-Feb	12621960
Comparison of finasteride and alpha-blockers as independent risk factors for erectile dysfunction.	2003 Jul-Aug	12918887
Is terazosin helpful in chronic prostatitis?	2003 Jun	12791224
Quinazoline-based alpha 1-adrenoceptor antagonists induce prostate cancer cell apoptosis via TGF-beta signalling and I kappa B alpha induction.	2003 May 19	12771931
Review: terazosin improves urologic symptoms in benign prostatic hyperplasia.	2003 May-Jun	12725629
Hormonal and morphologic evaluation of the effects of antiandrogens on the blood supply of the rat prostate.	2003 Nov	14624931
The alpha1-adrenoceptor antagonist terazosin induces prostate cancer cell death through a p53 and Rb independent pathway.	2003 Sep-Oct	12883741
Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs).	2004 Feb 23	14962589
Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia.	2004 Mar	14767264
Measurement of low-dose active pharmaceutical ingredient in a pharmaceutical blend using frequency-domain photon migration.	2004 Mar	14762902

Patents

Sample Use Guides

In Vivo Use Guide

for Hypertension: Initial dose: 1 mg orally once a day at bedtime; Maintenance dose: 1-5 mg orally once a day. Maximum dose: 20 mg per day. Usual Adult Dose for Benign Prostatic Hyperplasia: Initial dose: 1 mg orally once a day at bedtime. Maintenance dose: Increased in a stepwise fashion to 2 mg, 5 mg, or 10 mg once a day to achieve desired improvement of symptoms.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

TERAZOSIN HYDROCHLORIDE ANHYDROUS

Common Name

English

ABBOTT-45975 ANHYDROUS

Code

English

Terazosin hydrochloride anhydrous [WHO-DD]

Common Name

English

TERAZOSIN HYDROCHLORIDE, ANHYDROUS

Common Name

English

TERAZOSIN HCL

Common Name

English

TERAZOSIN HYDROCHLORIDE [MI]

Common Name

English

METHANONE, (4-(4-AMINO-6,7-DIMETHOXY-2-QUINAZOLINYL)-1-PIPERAZINYL)(TETRAHYDRO-2-FURANYL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

PIPERAZINE, 1-(4-AMINO-6,7-DIMETHOXY-2-QUINAZOLINYL)-4-((TETRAHYDRO-2-FURANYL)CARBONYL)-, MONOHYDROCHLORIDE

Common Name

English

6,7-DIMETHOXY-2-(4-(TETRAHYDROFURAN-2-YLCARBONYL)PIPERAZIN-1-YL)QUINAZOLIN-4-AMINE HYDROCHLORIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713