BUNAZOSIN HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H27N5O3.ClH
Molecular Weight	409.91
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCCC(=O)N1CCCN(CC1)C2=NC3=C(C=C(OC)C(OC)=C3)C(N)=N2

InChI

InChIKey=NBGBEUITCPENLJ-UHFFFAOYSA-N

InChI=1S/C19H27N5O3.ClH/c1-4-6-17(25)23-7-5-8-24(10-9-23)19-21-14-12-16(27-3)15(26-2)11-13(14)18(20)22-19;/h11-12H,4-10H2,1-3H3,(H2,20,21,22);1H

HIDE SMILES / InChI

Description
Sources: http://www.e-search.ne.jp/~jpr/PDF/EISAI03.PDF
Curator's Comment: description was created based on several sources, including: DOI: 10.1111/j.1527-3466.1988.tb00517.x | https://medikamio.com/de-de/medikamente/andante-3mg/pil | doi: 10.1016/B978-008055232-3.61351-0 | http://adisinsight.springer.com/drugs/800004823

Bunazosin (E-643) is a quinazoline derivative with a1-adrenoceptor blocking activity. It has been clinically used both as a systemic antihypertensive as well as an ocular hypotensive drug. The major adverse effect associated with the use of bunazosin is orthostatic hypotension or its consequences (e.g. dizziness). Others adverse effects include headache, sweating, nausea, dry mouth, abdominal pain, diarrhea, and constipation. The effects of Bunazosin may be enhanced by diuretics and other antihypertensive agents and decreased by Rifampicin.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor alpha-1 171 Target ID: CHEMBL1907610 Sources: http://www.e-search.ne.jp/~jpr/PDF/EISAI03.PDF	Blocker 555

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 575 Sources: http://www.e-search.ne.jp/~jpr/PDF/EISAI03.PDF	Primary	Approved 8583	Detantol@R Approved Use Detantol is indicated to treat hypertension.
Glaucoma 57 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15867947 http://adisinsight.springer.com/drugs/800004823	Primary	Phase III 665	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 175 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6102862	Primary	Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
15 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8929232/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6.1 μg/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.4 μg/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
11.4 μg/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
17.8 μg/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
14.6 μg/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
106 μg × h/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
86.6 μg × h/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
147.6 μg × h/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
220.5 μg × h/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
184 μg × h/L EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8929232/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
16 h EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
20.9 h EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

F_unbound

Value	Dose	Analyte	Population
3% EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3% EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
3% EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3% EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
3% EXPERIMENT https://link.springer.com/article/10.1007/BF03258454	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BUNAZOSIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
0.2 % single, ophthalmic Highest studied dose Dose: 0.2 % Route: ophthalmic Route: single Dose: 0.2 % Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/	Other AEs: conjunctival hyperemia... Other AEs: conjunctival hyperemia (moderately severe) Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/
12 mg 1 times / day multiple, oral Highest studied dose Dose: 12 mg, 1 times / day Route: oral Route: multiple Dose: 12 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9140673/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9140673/	Sources: https://pubmed.ncbi.nlm.nih.gov/9140673/
18 mg 1 times / day multiple, Highest studied dose Dose: 18 mg, 1 times / day Route: multiple Dose: 18 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7907871/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7907871/	Sources: https://pubmed.ncbi.nlm.nih.gov/7907871/
0.1 % single, ophthalmic Studied dose Dose: 0.1 % Route: ophthalmic Route: single Dose: 0.1 % Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/	Disc. AE: conjunctival hyperemia... AEs leading to discontinuation/dose reduction: conjunctival hyperemia (6 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/

AEs

AE	Significance	Dose	Population
conjunctival hyperemia	moderately severe	0.2 % single, ophthalmic Highest studied dose Dose: 0.2 % Route: ophthalmic Route: single Dose: 0.2 % Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/
conjunctival hyperemia	6 patients Disc. AE	0.1 % single, ophthalmic Studied dose Dose: 0.1 % Route: ophthalmic Route: single Dose: 0.1 % Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1684492/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Cav1.2 58

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 63	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyMzY2NDU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE4ODE4NSJ9fQ==

PubMed

Title	Date	PubMed
Restraint stress induces connexin-43 translocation via α-adrenoceptors in rat heart.	2010-11	20966593
Distinctive effects of carvedilol in the non-infarct zone: remodelling of the ligated rat heart linked to oxidative stress.	2009-11-26	19930840
Ocular hypotensive effects of anti-glaucoma agents in mice.	2009-10	19857101
New perspectives of infections in cardiovascular disease.	2009-05	20436849
Review of nifedipine GITS in the treatment of high risk patients with coronary artery disease and hypertension.	2009	19475779
[The use of andante in the therapy of insomnia].	2009	19365386
Ocular pharmacokinetic/pharmacodynamic modeling for multiple anti-glaucoma drugs.	2008-08	18670094
Possible mechanism of intraoperative floppy iris syndrome: a clinicopathological study.	2008-08	18653615
Comparison of the cardiac electrophysiological effects between doxazosin and bunazosin.	2008-07	18427952
Comparison of the cardiac effects between quinazoline-based alpha1-adrenoceptor antagonists on occlusion-reperfusion injury.	2008-03	17922254
Protective effects of carvedilol in murine model with the coxsackievirus B3-induced viral myocarditis.	2008-01	18209574
Effects of adrenergic and cholinergic antagonists on diameter of nasolacrimal drainage system.	2007-12	17579880
Role of alpha2C-adrenoceptors in the reduction of skin blood flow induced by local cooling in mice.	2007-09	17618305
The IOP-lowering effects and mechanism of action of tafluprost in prostanoid receptor-deficient mice.	2007-05	17124244
[Case of pigmentary glaucoma treated with medical therapy, laser treatment, and trabeculotomy].	2007-02	17338326
Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist.	2007-01	17188051
Beneficial effect of combination therapy with antihypertensive drugs in patients with hypertension.	2007	18650977
An alpha1-receptor blocker reduces plasma leptin levels in hypertensive patients with obesity and hyperleptinemia.	2006-10	17283868
Local regulation of skin blood flow during cooling involving presynaptic P2 purinoceptors in rats.	2006-07	16702991
Addition of or switch to topical bunazosin hydrochloride in elderly patients with normal-tension glaucoma: A one-year follow-up study.	2005-12-20	17013697
The effects of prostaglandin analogues on IOP in prostanoid FP-receptor-deficient mice.	2005-11	16249494
Effects of different alpha-1 adrenoceptor blockers on proximal urethral function using in vivo isovolumetric pressure changes.	2005-10	16428864
Alterations of alpha-adrenergic modulations of coronary microvascular tone in dogs with heart failure.	2005-06	15948090
Alpha1-receptor or adenosine A1-receptor dependent pathway alone is not sufficient but summation of these pathways is required to achieve an ischaemic preconditioning effect in rabbits.	2005-04	15810989
Amelioration of endothelin-1-induced optic nerve head ischemia by topical bunazosin.	2005-02	15814466
Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage.	2005	15867947
alpha1-Adrenergic receptor antagonists induce production of IL-18 and expression of ICAM-1 and CD40 in human monocytes.	2004-12-23	15614043
Effects of topically instilled bunazosin, an alpha1-adrenoceptor antagonist, on constrictions induced by phenylephrine and ET-1 in rabbit retinal arteries.	2004-11	15505054
Effects of bunazosin hydrochloride on ciliary muscle constriction and matrix metalloproteinase activities.	2004-08	15226660
Correlation between the additive effect of bunazosin and the response to latanoprost on intraocular pressure in patients with glaucoma treated with bunazosin as adjunctive therapy to latanoprost.	2004-07-01	16453191
Comparative study on the combined effects of bunazosin and nipradilol or timolol on intraocular pressure in normotensive rabbits.	2004-05-07	16365801
Ocular pharmacokinetic/ pharmacodynamic modeling for bunazosin after instillation into rabbits.	2004-05	15180332
Bunazosin hydrochloride reduces glutamate-induced neurotoxicity in rat primary retinal cultures.	2004-04-02	15019572
Evaluation of the additive effect of bunazosin on latanoprost in primary open-angle glaucoma.	2004-02-24	15692779
Efficacy of bunazosin hydrochloride 0.01% as adjunctive therapy of latanoprost or timolol.	2004-02	14704548
Effects of topically instilled bunazosin hydrochloride and other ocular hypotensive drugs on endothelin-1-induced constriction in rabbit retinal arteries.	2003-11-06	15486769
Additive effect of bunazosin on intraocular pressure when topically added to treatment with latanoprost in patients with glaucoma.	2003-09-12	12967873
[Effects of ocular hypotensive agents on the circadian rhythm in intraocular pressure in rabbits as measured by telemetry].	2003-09	14531310
Binding affinity of bunazosin, dorzolamide, and timolol to synthetic melanin.	2003-02-27	14767648
Amelioration by topical bunazosin hydrochloride of the impairment in ocular blood flow caused by nitric oxide synthase inhibition in rabbits.	2003-02	12648305
Effect of phenylephrine injected into the nucleus tractus solitarius of Sprague-Dawley rats and spontaneously hypertensive rats.	2002-08-15	12183010
Neuroprotective effects of nipradilol on purified cultured retinal ganglion cells.	2002-06	12140401
The alpha(1D)-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction.	2002-03	11901185
Different effects of carvedilol, metoprolol, and propranolol on left ventricular remodeling after coronary stenosis or after permanent coronary occlusion in rats.	2002-02-26	11864928
Purinergic modulation of vascular sympathetic neurotransmission.	2002-01	11855674
The renin-angiotensin and adrenergic nervous system in cardiac hypertrophy in fructose-fed rats.	2002-01	11824863
Noradrenaline stimulates 5-hydroxytryptamine release from mouse ileal tissues via alpha(2)-adrenoceptors.	2001-12-07	11740950
Neuroprotective effect and intraocular penetration of nipradilol, a beta-blocker with nitric oxide donative action.	2001-03	11222528
Orthostatic hypotension: how to avoid it during antihypertensive therapy.	1996-11	8931848
Effects of regression of left ventricular hypertrophy following atenolol or bunazosin therapy on ischemic cardiac function and myocardial metabolism in spontaneously hypertensive rats.	1991-12	1837320

Patents

Sample Use Guides

In Vivo Use Guide

3 to 9 mg once daily. The administration should be started at a dose of 3 mg once daily and the maximum daily dose of 9 mg should not be exceeded.

Route of Administration: Oral

In Vitro Use Guide

[3H]bunazosin binds specifically to rat brain preparation with a Bmax value of 84.6 fmol/mg protein and a Kd value of 0.59 nM.

Name

Type

Language

DETANTOL

Preferred Name

English

BUNAZOSIN HYDROCHLORIDE

Common Name

English

BUNAZOSIN HCL

Common Name

English

BUNAZOSIN HYDROCHLORIDE [JAN]

Common Name

English

BUNAZOSIN HYDROCHLORIDE [MI]

Common Name

English

E-643

Code

English

Bunazosin hydrochloride [WHO-DD]

Common Name

English

1-BUTANONE, 1-(4-(4-AMINO-6,7-DIMETHOXY-2-QUINAZOLINYL)HEXAHYDRO-1H-1,4-DIAZEPIN-1-YL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

BUNAZOSIN HYDROCHLORIDE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713