Tmic
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Record Information
Version2.0
Creation Date2009-07-30 17:58:43 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3487
Identification
Common NameBrimonidine
ClassSmall Molecule
DescriptionBrimonidine is only found in individuals that have used or taken this drug. It is a drug used to treat glaucoma. It acts via decreasing aqueous humor synthesis. [Wikipedia] A topical gel formulation, marketed under the name Mirvaso, was FDA approved on August 2013 for the treatment of rosacea. Brimonidine is an alpha adrenergic receptor agonist (primarily alpha-2). It has a peak ocular hypotensive effect occurring at two hours post-dosing. Fluorophotometric studies in animals and humans suggest that Brimonidine has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow.
Compound Type
  • Adrenergic alpha-2 Receptor Agonist
  • Adrenergic alpha-Agonist
  • Amide
  • Amine
  • Antihypertensive Agent
  • Bromide Compound
  • Drug
  • EENT Preparation
  • Metabolite
  • Organic Compound
  • Organobromide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline
Alphagan
Brimonidina
Brimonidine tartrate
Brimonidinum
Bromoxidine
Mirvaso
Chemical FormulaC11H10BrN5
Average Molecular Mass292.135 g/mol
Monoisotopic Mass291.012 g/mol
CAS Registry Number59803-98-4
IUPAC Name5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)quinoxalin-6-amine
Traditional Namebrimonidine
SMILESBrC1=C(NC2=NCCN2)C=CC2=C1N=CC=N2
InChI IdentifierInChI=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)
InChI KeyInChIKey=XYLJNLCSTIOKRM-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as quinoxalines. Quinoxalines are compounds containing a quinoxaline moiety, a bicyclic heterocycle made up of a benzene ring fused to a pyrazine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazanaphthalenes
Sub ClassBenzodiazines
Direct ParentQuinoxalines
Alternative Parents
Substituents
  • Quinoxaline
  • Aryl bromide
  • Aryl halide
  • Pyrazine
  • Benzenoid
  • 2-imidazoline
  • Heteroaromatic compound
  • Guanidine
  • Azacycle
  • Carboximidamide
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organobromide
  • Organohalogen compound
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point207.5°C
Boiling PointNot Available
SolubilitySoluble (1.5 mg/mL)
LogP1.7
Predicted Properties
PropertyValueSource
Water Solubility0.15 g/LALOGPS
logP1.27ALOGPS
logP1.37ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)8.32ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area62.2 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity68.49 m³·mol⁻¹ChemAxon
Polarizability25.74 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-03xr-0190000000-cd1ec9d5bf9d24fab607View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0006-0190000000-49c10e93a1977cbe01daView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0090000000-2f188927245c7fb3c618View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-1090000000-fdfdc04ca6c5f2b62c3eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9030000000-2d727aeec5962a767e61View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0090000000-91069ec802c3a06026d7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0090000000-7bd1085ed4367b683e29View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-2290000000-6351edb1d68a299dfd2dView in MoNA
Toxicity Profile
Route of ExposureMinimal systemic absorption occurs after ocular insertion. When the topical gel was applied to adult patients with facial erythema associated with rosacea, the plasma maximum concentration (Cmax) and area under the concentration-time curve (AUC) were 46 ± 62 pg/mL and 417 ± 264 pg.hr/mL, respectively. These values were reached on Day 15 of treatment.
Mechanism of ToxicityBrimonidine is an alpha adrenergic receptor agonist (primarily alpha-2). It has a peak ocular hypotensive effect occurring at two hours post-dosing. Fluorophotometric studies in animals and humans suggest that Brimonidine has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow. The topical gel reduces erythema through direct vasocontriction.
MetabolismMetabolized primarily by the liver. Route of Elimination: Urinary excretion is the major route of elimination of the drug and its metabolites. Half Life: 2 hours [ophthalmic solution]
Toxicity ValuesLD50: 50 mg/kg (oral, mice) LD50: 100 mg/kg (oral, rat)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThe ophthalmic solution is indicated for patients with open-angle glaucoma or ocular hypertension to lower intraocular pressure. The topical gel is indicated for the treatment of persistent (nontransient) facial erythema of rosacea in adults 18 years or older.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsOral LD50 is 50 mg/kg in mice and 100 mg/kg in rats.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00484
HMDB IDHMDB14627
PubChem Compound ID2435
ChEMBL IDCHEMBL844
ChemSpider ID2341
KEGG IDC07886
UniProt IDNot Available
OMIM ID
ChEBI ID3175
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBrimonidine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkBrimonidine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. FDA label
  2. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0027 uMNot AvailableBindingDB 34572
References
  1. Rauly I, Ailhaud M, Wurch T, Pauwels PJ: alpha(2A)-adrenoceptor: G(alphai1) protein-mediated pertussis toxin-resistant attenuation of G(s) coupling to the cyclic AMP pathway. Biochem Pharmacol. 2000 Jun 15;59(12):1531-8. [10799649 ]
  2. Wikberg-Matsson A, Simonsen U: Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55. [11481271 ]
  3. Meana JJ, Barturen F, Garro MA, Garcia-Sevilla JA, Fontan A, Zarranz JJ: Decreased density of presynaptic alpha 2-adrenoceptors in postmortem brains of patients with Alzheimer's disease. J Neurochem. 1992 May;58(5):1896-904. [1373179 ]
  4. Munk SA, Harcourt DA, Arasasingham PN, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Roberts D, Runde E, Williams L, Wheeler LA, Garst ME: Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. J Med Chem. 1997 Jan 3;40(1):18-23. [9016324 ]
  5. Reynen PH, Martin GR, Eglen RM, MacLennan SJ: Characterization of human recombinant alpha(2A)-adrenoceptors expressed in Chinese hamster lung cells using intracellular Ca(2+) changes: evidence for cross-talk between recombinant alpha(2A)- and native alpha(1)-adrenoceptors. Br J Pharmacol. 2000 Apr;129(7):1339-46. [10742289 ]
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular Weight:
49521.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.044 uMNot AvailableBindingDB 34572
References
  1. Trendelenburg AU, Philipp M, Meyer A, Klebroff W, Hein L, Starke K: All three alpha2-adrenoceptor types serve as autoreceptors in postganglionic sympathetic neurons. Naunyn Schmiedebergs Arch Pharmacol. 2003 Dec;368(6):504-12. Epub 2003 Nov 11. [14610637 ]
  2. Orito K, Kishi M, Imaizumi T, Nakazawa T, Hashimoto A, Mori T, Kambe T: alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator. Br J Pharmacol. 2001 Oct;134(4):763-70. [11606316 ]
  3. Zhang W, Ordway GA: The alpha2C-adrenoceptor modulates GABA release in mouse striatum. Brain Res Mol Brain Res. 2003 Apr 10;112(1-2):24-32. [12670699 ]
  4. Prinster SC, Holmqvist TG, Hall RA: Alpha2C-adrenergic receptors exhibit enhanced surface expression and signaling upon association with beta2-adrenergic receptors. J Pharmacol Exp Ther. 2006 Sep;318(3):974-81. Epub 2006 Jun 6. [16757535 ]
  5. Munk SA, Harcourt DA, Arasasingham PN, Burke JA, Kharlamb AB, Manlapaz CA, Padillo EU, Roberts D, Runde E, Williams L, Wheeler LA, Garst ME: Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. J Med Chem. 1997 Jan 3;40(1):18-23. [9016324 ]
General Function:
Epinephrine binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Trendelenburg AU, Philipp M, Meyer A, Klebroff W, Hein L, Starke K: All three alpha2-adrenoceptor types serve as autoreceptors in postganglionic sympathetic neurons. Naunyn Schmiedebergs Arch Pharmacol. 2003 Dec;368(6):504-12. Epub 2003 Nov 11. [14610637 ]
  2. Bohmann C, Schollmeyer P, Rump LC: Methoxamine inhibits noradrenaline release through activation of alpha 1- and alpha 2-adrenoceptors in rat isolated kidney: involvement of purines and prostaglandins. Naunyn Schmiedebergs Arch Pharmacol. 1993 Mar;347(3):273-9. [8097565 ]