BRIMONIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H10BrN5
Molecular Weight	292.1345
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cc2c(c(c1NC3=NCCN3)Br)nccn2

InChI

InChIKey=XYLJNLCSTIOKRM-UHFFFAOYSA-N

InChI=1S/C11H10BrN5/c12-9-7(17-11-15-5-6-16-11)1-2-8-10(9)14-4-3-13-8/h1-4H,5-6H2,(H2,15,16,17)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021262s020,021770s004lbl.pdf
Curator's Comment:: description was created based on several sources, including: https://www.drugs.com/mtm/brimonidine-ophthalmic.html http://www.drugbank.ca/drugs/DB00484 DOI: 10.1002/9781118541203.xen125

Brimonidine reduces the amount of fluid in the eye, which decreases pressure inside the eye. Brimonidine ophthalmic (for the eyes) is used to treat open-angle glaucoma or ocular hypertension (high pressure inside the eye). Brimonidine is an alpha adrenergic receptor agonist (primarily alpha-2). Fluorophotometric studies in animals and humans suggest that Brimonidine has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow. Adverse reactions occurring in approximately 1020% of the subjects receiving brimonidine ophthalmic solution (0.1-0.2%) included: allergic conjunctivitis, conjunctival hyperemia, and eye pruritus. Because Brimonidine may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with Brimonidine is advised.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-2A adrenergic receptor 24 Target ID: P08913 Gene ID: 150.0 Gene Symbol: ADRA2A Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00484 \| https://www.ncbi.nlm.nih.gov/pubmed/14610637 \| https://www.ncbi.nlm.nih.gov/pubmed/11606316	Agonist 2451
Alpha-2B adrenergic receptor 13 Target ID: P18089 Gene ID: 151.0 Gene Symbol: ADRA2B Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00484 \| https://www.ncbi.nlm.nih.gov/pubmed/8097565	Agonist 2451
Alpha-2C adrenergic receptor 11 Target ID: P18825 Gene ID: 152.0 Gene Symbol: ADRA2C Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00484 \| https://www.ncbi.nlm.nih.gov/pubmed/11481271	Agonist 2451

Conditions

Condition	Modality	Highest Phase	Product
Open-angle glaucoma 50 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021262s020,021770s004lbl.pdf	Primary	Approved 7968	ALPHAGAN P Approved Use Brimonidine Tartrate Ophthalmic Solution is indicated for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. The IOP lowering efficacy of Brimonidine Tartrate Ophthalmic Solution diminishes over time in some patients. This loss of effect appears with a variable time of onset in each patient and should be closely monitored. Launch Date 1.12440954E12
Ocular hypertension 49 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021262s020,021770s004lbl.pdf	Primary	Approved 7968	ALPHAGAN P Approved Use Brimonidine Tartrate Ophthalmic Solution is indicated for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. The IOP lowering efficacy of Brimonidine Tartrate Ophthalmic Solution diminishes over time in some patients. This loss of effect appears with a variable time of onset in each patient and should be closely monitored. Launch Date 1.12440954E12
Persistent (nontransient) facial erythema of rosacea 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204708s005lbl.pdf	Primary	Approved 7968	MIRVASO Approved Use Brimonidine topical gel, 0.33% is an alpha adrenergic agonist indicated for the topical treatment of persistent (nontransient) erythema of rosacea in adults 18 years of age or older. Launch Date 1.37712959E12

C_max

Value	Dose	Co-administered	Analyte	Population
73 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021764s005lbl.pdf	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		BRIMONIDINE TARTRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
375 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021764s005lbl.pdf	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		BRIMONIDINE TARTRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021764s005lbl.pdf	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		BRIMONIDINE TARTRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.33 % single, oromucosal Dose: 0.33 % Route: oromucosal Route: single Dose: 0.33 % Sources: https://pubmed.ncbi.nlm.nih.gov/28297016	unhealthy, 4 years n = 1 Health Status: unhealthy Age Group: 4 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28297016	Other AEs: Bradycardia, Somnolence... Other AEs: Bradycardia Somnolence Sources: https://pubmed.ncbi.nlm.nih.gov/28297016
0.5 % single, ophthalmic Dose: 0.5 % Route: ophthalmic Route: single Dose: 0.5 % Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-490S007_Brimonidine%20Tartrate%20Ophthalmic_medr.pdf Page: p. 19	unhealthy, 4.8 years (range: 2-7 years) n = 38 Health Status: unhealthy Age Group: 4.8 years (range: 2-7 years) Sex: M+F Population Size: 38 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-490S007_Brimonidine%20Tartrate%20Ophthalmic_medr.pdf Page: p. 19	Disc. AE: Somnolence... AEs leading to discontinuation/dose reduction: Somnolence Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-490S007_Brimonidine%20Tartrate%20Ophthalmic_medr.pdf Page: p. 19
0.33 % 1 times / day steady, topical Recommended Dose: 0.33 %, 1 times / day Route: topical Route: steady Dose: 0.33 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204708Orig1s000MedR.pdf Page: p. 66	unhealthy, adult n = 330 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 330 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204708Orig1s000MedR.pdf Page: p. 66	Disc. AE: Contact dermatitis, Erythema... AEs leading to discontinuation/dose reduction: Contact dermatitis (0.6%) Erythema (0.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204708Orig1s000MedR.pdf Page: p. 66

AEs

AE	Significance	Dose	Population
Bradycardia		0.33 % single, oromucosal Dose: 0.33 % Route: oromucosal Route: single Dose: 0.33 % Sources: https://pubmed.ncbi.nlm.nih.gov/28297016	unhealthy, 4 years n = 1 Health Status: unhealthy Age Group: 4 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28297016
Somnolence		0.33 % single, oromucosal Dose: 0.33 % Route: oromucosal Route: single Dose: 0.33 % Sources: https://pubmed.ncbi.nlm.nih.gov/28297016	unhealthy, 4 years n = 1 Health Status: unhealthy Age Group: 4 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28297016
Somnolence	Disc. AE	0.5 % single, ophthalmic Dose: 0.5 % Route: ophthalmic Route: single Dose: 0.5 % Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-490S007_Brimonidine%20Tartrate%20Ophthalmic_medr.pdf Page: p. 19	unhealthy, 4.8 years (range: 2-7 years) n = 38 Health Status: unhealthy Age Group: 4.8 years (range: 2-7 years) Sex: M+F Population Size: 38 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-490S007_Brimonidine%20Tartrate%20Ophthalmic_medr.pdf Page: p. 19
Erythema	0.3% Disc. AE	0.33 % 1 times / day steady, topical Recommended Dose: 0.33 %, 1 times / day Route: topical Route: steady Dose: 0.33 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204708Orig1s000MedR.pdf Page: p. 66	unhealthy, adult n = 330 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 330 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204708Orig1s000MedR.pdf Page: p. 66
Contact dermatitis	0.6% Disc. AE	0.33 % 1 times / day steady, topical Recommended Dose: 0.33 %, 1 times / day Route: topical Route: steady Dose: 0.33 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204708Orig1s000MedR.pdf Page: p. 66	unhealthy, adult n = 330 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 330 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204708Orig1s000MedR.pdf Page: p. 66

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3175	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3175
ChemicalBook	CB9111370	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9111370
MolPort	MolPort-003-959-841	https://www.molport.com/shop/molecule-link/MolPort-003-959-841
ZINC	ZINC000021303210	http://zinc15.docking.org/substances/ZINC000021303210
eMolecules	595250	https://www.emolecules.com/cgi-bin/more?vid=595250

PubMed

Title	Date	PubMed
Neuroprotective effects of alpha(2)-selective adrenergic agonists against ischemia-induced retinal ganglion cell death.	2001 Aug	11481275
Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries.	2001 Aug	11481271
The adverse effect of perioperative brimonidine tartrate 0.2% on flap adherence and enhancement rates in laser in situ keratomileusis patients.	2001 Aug	11470696
The impact of new drugs on management of glaucoma in Scotland: observational study.	2001 Dec 15	11744564
Noradrenaline stimulates 5-hydroxytryptamine release from mouse ileal tissues via alpha(2)-adrenoceptors.	2001 Dec 7	11740950
Comparison of the clinical success and quality-of-life impact of brimonidine 0.2% and betaxolol 0.25 % suspension in patients with elevated intraocular pressure.	2001 Jul	11519768
Role of the extracellular signal-regulated kinase (Erk) signal transduction cascade in alpha(2) adrenoceptor-mediated vasoconstriction in porcine palmar lateral vein.	2001 Jul	11454659
Disturbance of the prejunctional modulation of cholinergic neurotransmission during chronic granulomatous inflammation of the mouse ileum.	2001 Jul	11429394
The effect of adrenergic compounds on neurogenic dural vasodilatation.	2001 Jul 13	11470260
Role of alpha(2)-adrenoceptors in the sympathetic inhibition of motility reflexes of guinea-pig ileum.	2001 Jul 15	11454964
Clinical and economic impact of new trends in glaucoma treatment.	2001 Jul 26	11549985
Brimonidine (Alphagan): a clinical profile four years after launch.	2001 Jul-Sep	11592536
Influence of topical brimonidine on visual field in glaucoma.	2001 Jul-Sep	11592534
Brimonidine's neuroprotective effects against transient ischaemia-induced retinal ganglion cell death.	2001 Jul-Sep	11592529
Apoptosis and anti-apoptosis signalling in glaucomatous retinopathy.	2001 Jul-Sep	11592526
Effectiveness and safety of brimonidine as adjunctive therapy for patients with elevated intraocular pressure in a large, open-label community trial.	2001 Jun	11442187
Effect of brimonidine tartrate on ocular hemodynamics in healthy volunteers.	2001 Jun	11436940
Brimonidine 0.2% given two or three times daily versus timolol maleate 0.5% in primary open-angle glaucoma.	2001 Jun	11384568
Topically applied clonidine protects the rat retina from ischaemia/reperfusion by stimulating alpha(2)-adrenoceptors and not by an action on imidazoline receptors.	2001 Jun 15	11516418
The alpha(1A)-adrenoceptor subtype mediates contraction in rat femoral resistance arteries.	2001 Jun 22	11430923
Brimonidine and inhibition of nitrite production in isolated porcine ciliary processes.	2001 May	11417333
Ca2+ influx mediates enhanced alpha2-adrenergic contraction in aortas from rats treated with NOS inhibitor.	2001 Nov	11668088
Functional characterization of alpha1-adrenoceptor subtypes in human subcutaneous resistance arteries.	2001 Nov	11602687
Circadian change of adenylate cyclase activity in rabbit ciliary processes.	2001 Oct	11852425
[Prevention of early postoperative increase in intraocular pressure after phacoemulsification. Comparison of different antiglaucoma drugs].	2001 Oct	11699314
[Prospects for neuroprotective glaucoma therapy].	2001 Oct	11699312
[Brimonidine absorption and release from 1. Day acuvue disposable contact lenses].	2001 Oct	11685677
alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator.	2001 Oct	11606316
[Experience with topical brimonidine in the treatment of glaucomas].	2001 Sep	11680422
Effects of central imidazolinergic and alpha2-adrenergic activation on water intake.	2001 Sep	11514843
Effects of acute and chronic ethanol administration on the response of mouse adipose tissue hormone-sensitive lipase to alpha(2)-adrenoceptor activation bu UK 14304.	2001 Sep-Oct	11524302
Failure of naloxone to reverse brimonidine-induced coma in an infant.	2002 Apr	12006970
The efficacy of brimonidine in preventing intraocular pressure elevation in the provocative test for primary angle-closure glaucoma.	2002 Apr	12002673
Intraocular pressure-lowering effects of latanoprost and brimonidine therapy in patients with open-angle glaucoma or ocular hypertension: a randomized observer-masked multicenter study.	2002 Apr	11912355
Effects of acute and subchronic administration of dexefaroxan, an alpha(2)-adrenoceptor antagonist, on memory performance in young adult and aged rodents.	2002 Apr	11907173
Distribution of brimonidine into anterior and posterior tissues of monkey, rabbit, and rat eyes.	2002 Apr	11901096
Lysophosphatidylcholine potentiates vascular contractile responses in rat aorta via activation of tyrosine kinase.	2002 Feb	11834627
Substance P, insulinlike growth factor 1, and surface healing.	2002 Feb	11831929
Three-month comparison of brimonidine and latanoprost as adjunctive therapy in glaucoma and ocular hypertension patients uncontrolled on beta-blockers: tolerance and peak intraocular pressure lowering.	2002 Feb	11825814
Clinical effects of brimonidine ophthalmic drops ingestion in 52 dogs.	2002 Feb	11824775
A short term study of the additive effect of timolol and brimonidine on intraocular pressure.	2002 Jan	11913886
Presynaptic modulation of cholinergic neurotransmission in the human proximal stomach.	2002 Jan	11786489
alpha(2C)-Adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy.	2002 Jan	11752127
A comparison of the short-term hypotensive effects and side effects of unilateral brimonidine and apraclonidine in patients with elevated intraocular pressure.	2002 Jan-Feb	11901288
Pre- and postjunctional alpha(2)-adrenergic receptors in fetal and adult ovine cerebral arteries.	2002 Jun	12010747
Delayed hypersensitivity to brimonidine tartrate 0.2% associated with high intraocular pressure.	2002 Mar	11988811
Analysis of the effects of graded levels of hypoxia on noradrenaline-evoked contraction in the rat iliac artery in vitro.	2002 Mar	11856962
Release inhibitory receptors activation favours the A2A-adenosine receptor-mediated facilitation of noradrenaline release in isolated rat tail artery.	2002 May	12010771
The effects of new topical treatments on management of glaucoma in Scotland: an examination of ophthalmological health care.	2002 May	11973253
alpha 2B-adrenergic receptor activates MAPK via a pathway involving arachidonic acid metabolism, matrix metalloproteinases, and epidermal growth factor receptor transactivation.	2002 May 31	11891218

Patents

Sample Use Guides

In Vivo Use Guide

One drop in the affected eye(s), three times daily, approximately 8 hours apart

Route of Administration: Topical

In Vitro Use Guide

Cells were pretreated for 6 h with different doses of Brimonidine tartrate 0.1% (1/2×, 1×, 5×, 10×), followed by a 24-h exposure to 100 μM of Hydroquinone. The ROS levels decreased at 1×, 5×, and 10× doses of Brimonidine in ARPE-19 but only at 10× on MIO-M1 cells.

Name

Type

Language

BRIMONIDINE

Official Name

English

AGN-190342 FREE BASE

Code

English

5-BROMO-6-(2-IMIDAZOLIN-2-YLAMINO)QUINOXALINE D-TARTRATE (1:1).

Systematic Name

English

BRIMONIDINE [WHO-DD]

Common Name

English

BRIMONIDINE [VANDF]

Common Name

English

UK-1430418 FREE BASE

Code

English

BRIMONIDINE [INN]

Common Name

English

6-QUINOXALINAMINE, 5-BROMO-N-(4,5-DIHYDRO-1H-IMIDAZOL-2-YL)-, (S-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (1:1)

Systematic Name

English

UK-14304

Code

English

BRIMONIDINE [MI]

Common Name

English

NSC-318825

Code

English

Classification Tree Code System Code

WHO-VATC

QS01EA05