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Details

Stereochemistry RACEMIC
Molecular Formula C23H25N5O5.ClH
Molecular Weight 487.936
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DOXAZOSIN HYDROCHLORIDE

SMILES

Cl.COC1=CC2=NC(=NC(N)=C2C=C1OC)N3CCN(CC3)C(=O)C4COC5=CC=CC=C5O4

InChI

InChIKey=AQAZIYFEPYHLHC-UHFFFAOYSA-N
InChI=1S/C23H25N5O5.ClH/c1-30-18-11-14-15(12-19(18)31-2)25-23(26-21(14)24)28-9-7-27(8-10-28)22(29)20-13-32-16-5-3-4-6-17(16)33-20;/h3-6,11-12,20H,7-10,13H2,1-2H3,(H2,24,25,26);1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C23H25N5O5
Molecular Weight 451.4751
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Doxazosin mesylate is a quinazoline compound sold by Pfizer under the brand name CARDURA. CARDURA is indicated for the treatment of both the urinary outflow obstruction and obstructive and irritative symptoms associated with BPH: obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning). CARDURA may be used in all BPH patients whether hypertensive or normotensive. In patients with hypertension and BPH, both conditions were effectively treated with CARDURA monotherapy. CARDURA provides rapid improvement in symptoms and urinary flow rate in 66–71% of patients. CARDURA is also indicated for the treatment of hypertension. CARDURA may be used alone or in combination with diuretics, beta-adrenergic blocking agents, calcium channel blockers, or angiotensin-converting enzyme inhibitors. Doxazosin acts by inhibiting the postsynaptic alpha(1)-adrenoceptors on vascular smooth muscle. This inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation.

Originator

Curator's Comment: # Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CARDURA

Approved Use

INDICATIONS AND USAGE A. Benign Prostatic Hyperplasia (BPH). CARDURA is indicated for the treatment of both the urinary outflow obstruction and obstructive and irritative symptoms associated with BPH: obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning). CARDURA may be used in all BPH patients whether hypertensive or normotensive. In patients with hypertension and BPH, both conditions were effectively treated with CARDURA monotherapy. CARDURA provides rapid improvement in symptoms and urinary flow rate in 66–71% of patients. Sustained improvements with CARDURA were seen in patients treated for up to 14 weeks in double-blind studies and up to 2 years in open-label studies. B. Hypertension. CARDURA is also indicated for the treatment of hypertension. CARDURA may be used alone or in combination with diuretics, beta-adrenergic blocking agents, calcium channel blockers, or angiotensin-converting enzyme inhibitors.

Launch Date

6.5750401E11
Primary
CARDURA

Approved Use

INDICATIONS AND USAGE A. Benign Prostatic Hyperplasia (BPH). CARDURA is indicated for the treatment of both the urinary outflow obstruction and obstructive and irritative symptoms associated with BPH: obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning). CARDURA may be used in all BPH patients whether hypertensive or normotensive. In patients with hypertension and BPH, both conditions were effectively treated with CARDURA monotherapy. CARDURA provides rapid improvement in symptoms and urinary flow rate in 66–71% of patients. Sustained improvements with CARDURA were seen in patients treated for up to 14 weeks in double-blind studies and up to 2 years in open-label studies. B. Hypertension. CARDURA is also indicated for the treatment of hypertension. CARDURA may be used alone or in combination with diuretics, beta-adrenergic blocking agents, calcium channel blockers, or angiotensin-converting enzyme inhibitors.

Launch Date

6.5750401E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
9.7 ng/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
13.6 ng/mL
1 mg 1 times / day steady-state, oral
dose: 1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
14.3 ng/mL
1 mg 1 times / day steady-state, oral
dose: 1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
151.7 ng/mL
16 mg 1 times / day steady-state, oral
dose: 16 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
42.3 ng/mL
4 mg 1 times / day steady-state, oral
dose: 4 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
65.5 ng/mL
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
162 ng × h/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
268 ng × h/mL
1 mg 1 times / day steady-state, oral
dose: 1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.9 h
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
15 h
1 mg 1 times / day steady-state, oral
dose: 1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
11.9 h
1 mg 1 times / day steady-state, oral
dose: 1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11.6 h
16 mg 1 times / day steady-state, oral
dose: 16 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
12.8 h
4 mg 1 times / day steady-state, oral
dose: 4 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8.3 h
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DOXAZOSIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
60 mg single, oral
Overdose
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
healthy, 19 years
n = 1
Health Status: healthy
Age Group: 19 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Sinus tachycardia...
AEs leading to
discontinuation/dose reduction:
Sinus tachycardia (1 patient)
Sources:
16 mg single, oral (max)
Highest studied dose
Dose: 16 mg
Route: oral
Route: single
Dose: 16 mg
Sources:
unhealthy, adult
n = 665
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: unknown
Population Size: 665
Sources:
DLT: Postural edema...
Dose limiting toxicities:
Postural edema (2.7%)
Sources:
4 mg 1 times / day steady, oral
Recommended
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
healthy, adult
n = 35
Health Status: healthy
Age Group: adult
Sex: unknown
Population Size: 35
Sources:
Disc. AE: Orthostatic dizziness...
AEs leading to
discontinuation/dose reduction:
Orthostatic dizziness (1 patient)
Sources:
16 mg 1 times / day steady, oral (max)
Highest studied dose
Dose: 16 mg, 1 times / day
Route: oral
Route: steady
Dose: 16 mg, 1 times / day
Sources:
unhealthy, mean 59 years
n = 97
Health Status: unhealthy
Condition: Hypertension
Age Group: mean 59 years
Sex: M+F
Population Size: 97
Sources:
Disc. AE: Fatigue, Urinary incontinence...
Other AEs: Rhinitis...
AEs leading to
discontinuation/dose reduction:
Fatigue (3 patients)
Urinary incontinence (2 patients)
Other AEs:
Rhinitis (1 patient)
Sources:
8 mg 1 times / day steady, oral
Dose: 8 mg, 1 times / day
Route: oral
Route: steady
Dose: 8 mg, 1 times / day
Sources:
unhealthy
n = 22
Health Status: unhealthy
Condition: cocaine dependence
Population Size: 22
Sources:
Other AEs: Nausea, Constipation...
Other AEs:
Nausea (below serious, 2 patients)
Constipation (below serious, 1 patient)
Allergy (below serious, 1 patient)
Dizziness (below serious, 1 patient)
Numbness (below serious, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Sinus tachycardia 1 patient
Disc. AE
60 mg single, oral
Overdose
Dose: 60 mg
Route: oral
Route: single
Dose: 60 mg
Sources:
healthy, 19 years
n = 1
Health Status: healthy
Age Group: 19 years
Sex: F
Population Size: 1
Sources:
Postural edema 2.7%
DLT
16 mg single, oral (max)
Highest studied dose
Dose: 16 mg
Route: oral
Route: single
Dose: 16 mg
Sources:
unhealthy, adult
n = 665
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: unknown
Population Size: 665
Sources:
Orthostatic dizziness 1 patient
Disc. AE
4 mg 1 times / day steady, oral
Recommended
Dose: 4 mg, 1 times / day
Route: oral
Route: steady
Dose: 4 mg, 1 times / day
Sources:
healthy, adult
n = 35
Health Status: healthy
Age Group: adult
Sex: unknown
Population Size: 35
Sources:
Rhinitis 1 patient
16 mg 1 times / day steady, oral (max)
Highest studied dose
Dose: 16 mg, 1 times / day
Route: oral
Route: steady
Dose: 16 mg, 1 times / day
Sources:
unhealthy, mean 59 years
n = 97
Health Status: unhealthy
Condition: Hypertension
Age Group: mean 59 years
Sex: M+F
Population Size: 97
Sources:
Urinary incontinence 2 patients
Disc. AE
16 mg 1 times / day steady, oral (max)
Highest studied dose
Dose: 16 mg, 1 times / day
Route: oral
Route: steady
Dose: 16 mg, 1 times / day
Sources:
unhealthy, mean 59 years
n = 97
Health Status: unhealthy
Condition: Hypertension
Age Group: mean 59 years
Sex: M+F
Population Size: 97
Sources:
Fatigue 3 patients
Disc. AE
16 mg 1 times / day steady, oral (max)
Highest studied dose
Dose: 16 mg, 1 times / day
Route: oral
Route: steady
Dose: 16 mg, 1 times / day
Sources:
unhealthy, mean 59 years
n = 97
Health Status: unhealthy
Condition: Hypertension
Age Group: mean 59 years
Sex: M+F
Population Size: 97
Sources:
Allergy below serious, 1 patient
8 mg 1 times / day steady, oral
Dose: 8 mg, 1 times / day
Route: oral
Route: steady
Dose: 8 mg, 1 times / day
Sources:
unhealthy
n = 22
Health Status: unhealthy
Condition: cocaine dependence
Population Size: 22
Sources:
Constipation below serious, 1 patient
8 mg 1 times / day steady, oral
Dose: 8 mg, 1 times / day
Route: oral
Route: steady
Dose: 8 mg, 1 times / day
Sources:
unhealthy
n = 22
Health Status: unhealthy
Condition: cocaine dependence
Population Size: 22
Sources:
Dizziness below serious, 1 patient
8 mg 1 times / day steady, oral
Dose: 8 mg, 1 times / day
Route: oral
Route: steady
Dose: 8 mg, 1 times / day
Sources:
unhealthy
n = 22
Health Status: unhealthy
Condition: cocaine dependence
Population Size: 22
Sources:
Numbness below serious, 1 patient
8 mg 1 times / day steady, oral
Dose: 8 mg, 1 times / day
Route: oral
Route: steady
Dose: 8 mg, 1 times / day
Sources:
unhealthy
n = 22
Health Status: unhealthy
Condition: cocaine dependence
Population Size: 22
Sources:
Nausea below serious, 2 patients
8 mg 1 times / day steady, oral
Dose: 8 mg, 1 times / day
Route: oral
Route: steady
Dose: 8 mg, 1 times / day
Sources:
unhealthy
n = 22
Health Status: unhealthy
Condition: cocaine dependence
Population Size: 22
Sources:
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer








Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Quality-of-life assessment in patients with benign prostatic hyperplasia: effects of various interventions.
2001
Efficacy and tolerability of drugs for treatment of benign prostatic hyperplasia.
2001
Effects of two atypical neuroleptics, olanzapine and risperidone, on the function of the urinary bladder and the external urethral sphincter in anesthetized rats.
2001
Is postural hypotension a real problem with antihypertensive medication?
2001
A comparison of selected antihypertensives and the use of conventional vs ambulatory blood pressure in the detection and treatment of hypertension.
2001
Discontinuation of alpha-blockade after initial treatment with finasteride and doxazosin in men with lower urinary tract symptoms and clinical evidence of benign prostatic hyperplasia.
2001 Aug
Lessons learned from prematurely terminated clinical trials.
2001 Aug
Apoptotic activity of doxazosin on prostate stroma in vitro is mediated through an autocrine expression of TGF-beta1.
2001 Aug 1
Meta-analysis of studies using selective alpha1-blockers in patients with hypertension and type 2 diabetes.
2001 Dec
5alpha-reductase inhibitors: what role should they play?
2001 Dec
Low-dose ACE with alpha- or beta-adrenergic receptor inhibitors have beneficial SHR cardiovascular effects.
2001 Jan
On call. I'm a 76-year-old man with an enlarged prostate. I've been taking Cardura and it's helped a lot, but my doctor stopped it because he said a study found the drug could cause heart failure. Now I'm getting up three or four times a night again. Is Cadura safe?
2001 Jul
Safety and availability of doxazosin in treating hypertensive patients with chronic renal failure.
2001 Jul
Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects.
2001 Jul
[Doxazosin and soluble guanylate cyclase in a rat model of hypertension].
2001 Jul
Role of alpha1-blockade in congenital long QT syndrome: investigation by exercise stress test.
2001 Jul
Reduction of human prostate tumor vascularity by the alpha1-adrenoceptor antagonist terazosin.
2001 Jul 1
Doxazosin added to single-drug therapy in hypertensive patients with benign prostatic hypertrophy.
2001 Jul-Aug
Low-dose alpha/beta blockade in the treatment of essential hypertension.
2001 Jun
Voltammetric determination of doxazosin in tablets using rotating platinum electrode.
2001 Jun
US FDA weighs options for warning on antihypertensive drug.
2001 Jun 2
Structure-activity studies for a novel series of bicyclic substituted hexahydrobenz[e]isoindole alpha1A adrenoceptor antagonists as potential agents for the symptomatic treatment of benign prostatic hyperplasia.
2001 Jun 7
[Long-term therapy of benign prostatic hyperplasia. Our experience].
2001 Mar
Update in pharmacologic treatment of hypertension.
2001 May
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
Effect of antihypertensive therapy on renal artery structure in type 2 diabetic rats with hypertension.
2001 May
Reversible renal impairment induced by treatment with the angiotensin II receptor antagonist candesartan in a patient with bilateral renal artery stenosis.
2001 May 17
[Alpha-blockers in therapy of arterial hypertension. No longer the drug of first choice].
2001 May 31
[Doksazozin "Cardura" in acute urinary retention caused by benign prostatic hyperplasia].
2001 May-Jun
Effects of antihypertensive agents on blood pressure during exercise.
2001 Nov
Doxazosin and congestive heart failure.
2001 Nov 1
Ventricular production of natriuretic peptides and ventricular structural remodeling in hypertensive heart failure.
2001 Oct
A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease.
2001 Oct
Warning for antihypertensive drug?
2001 Oct 6
Doxazosin reduces prevalence of small dense low density lipoprotein and remnant-like particle cholesterol levels in nondiabetic and diabetic hypertensive patients.
2001 Sep
Heart lines. Cardura update.
2001 Sep
The choice of antihypertensive drugs in patients with erectile dysfunction.
2002
Observational multicentric trial performed with doxazosin: evaluation of sexual effects on patients with diagnosed benign prostatic hyperplasia.
2002
Influence of the alpha-1-adrenergic receptor blocker doxazosin on exercise-induced hyperkalemia in hemodialysis patients.
2002
[Doxazosin, of modified liberation, in hemodialyzed patients].
2002 Apr
Efficacy and safety of doxazosin for perioperative management of patients with pheochromocytoma.
2002 Aug
Medical therapy for benign prostatic hyperplasia progression.
2002 Aug
Critical evaluation of the problem of chronic urinary retention after orthotopic bladder substitution in women.
2002 Aug
Double-blind, crossover, comparative study of doxazosin and enalapril in the treatment of hypertension in renal transplant patients under cyclosporine immunosuppression.
2002 Feb
The use of alpha-adrenoceptor antagonists in lower urinary tract disease.
2002 Feb
Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.
2002 Feb
Psychological characteristics and responses to antihypertensive drug therapy.
2002 Jan-Feb
Treatment of hypertension in the elderly.
2002 Jan-Feb
Reduction of the soluble cyclic GMP vasorelaxing system in the vascular wall of stroke-prone spontaneously hypertensive rats: effect of the alpha1 -receptor blocker doxazosin.
2002 Mar
Premature termination of clinical trials--lessons learned.
2002 May-Jun
Patents

Patents

Sample Use Guides

Usual Adult Dose for Hypertension Initial dose: 1 mg orally once a day. Maintenance dose: 1 to 16 mg orally once a day. Usual Adult Dose for Benign Prostatic Hyperplasia Initial dose: Immediate-release: 1 mg orally once a day. Extended-release: 4 mg orally once a day with breakfast Maintenance dose: Immediate-release: 1 to 8 mg orally once a day. Extended-release: 4 to 8 mg orally once a day with breakfast. Depending on the patient's symptomatic response and tolerability, the dose may be increased to 8 mg (the maximum recommended dose). The recommended titration interval is 3 to 4 weeks.
Route of Administration: Oral
In Vitro Use Guide
Ring segments of splanchnic, peripheral, coronary, pulmonary and uterine conduit arteries obtained during surgery were studied in tissue baths. Resistance arteries dissected from various sites were studied in a myograph. Both conduit and resistance vessels contracted in response to the alpha 1-agonist phenylephrine (10(-7) to 10(-4) mol/l), an effect that was antagonized by the alpha 1-antagonist doxazosin (10(-8) to 10(-6) mol/l).
Substance Class Chemical
Created
by admin
on Thu Jul 06 17:03:23 UTC 2023
Edited
by admin
on Thu Jul 06 17:03:23 UTC 2023
Record UNII
Y9EDC2483R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DOXAZOSIN HYDROCHLORIDE
Common Name English
PIPERAZINE, 1-(4-AMINO-6,7-DIMETHOXY-2-QUINAZOLINYL)-4-((2,3-DIHYDRO-1,4-BENZODIOXIN-2-YL)CARBONYL)-, MONOHYDROCHLORIDE
Common Name English
METHANONE, (4-(4-AMINO-6,7-DIMETHOXY-2-QUINAZOLINYL)-1-PIPERAZINYL)(2,3-DIHYDRO-1,4-BENZODIOXIN-2-YL)-, HYDROCHLORIDE (1:1)
Systematic Name English
Code System Code Type Description
EPA CompTox
DTXSID00469077
Created by admin on Thu Jul 06 17:03:23 UTC 2023 , Edited by admin on Thu Jul 06 17:03:23 UTC 2023
PRIMARY
CAS
70918-01-3
Created by admin on Thu Jul 06 17:03:23 UTC 2023 , Edited by admin on Thu Jul 06 17:03:23 UTC 2023
PRIMARY
FDA UNII
Y9EDC2483R
Created by admin on Thu Jul 06 17:03:23 UTC 2023 , Edited by admin on Thu Jul 06 17:03:23 UTC 2023
PRIMARY
PUBCHEM
11591230
Created by admin on Thu Jul 06 17:03:23 UTC 2023 , Edited by admin on Thu Jul 06 17:03:23 UTC 2023
PRIMARY
CAS
105314-71-4
Created by admin on Thu Jul 06 17:03:23 UTC 2023 , Edited by admin on Thu Jul 06 17:03:23 UTC 2023
NON-SPECIFIC STOICHIOMETRY
Related Record Type Details
PARENT -> SALT/SOLVATE