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Identification
NameApraclonidine
Accession NumberDB00964  (APRD00012)
TypeSmall Molecule
GroupsApproved
Description

Apraclonidine, also known as iopidine, is a sympathomimetic used in glaucoma therapy. It is an alpha2-adrenergic agonist.

Structure
Thumb
Synonyms
SynonymLanguageCode
4-AminoclonidineNot AvailableNot Available
ApraclonidinaSpanishINN
ApraclonidinumLatinINN
Salts
Name/CAS Structure Properties
Apraclonidine Hydrochloride
Thumb
  • InChI Key: OTQYGBJVDRBCHC-UHFFFAOYSA-N
  • Monoisotopic Mass: 280.004929493
  • Average Mass: 281.569
DBSALT000819
Brand names
NameCompany
IopidineNot Available
Brand mixturesNot Available
Categories
CAS number66711-21-5
WeightAverage: 245.109
Monoisotopic: 244.028251754
Chemical FormulaC9H10Cl2N4
InChI KeyIEJXVRYNEISIKR-UHFFFAOYSA-N
InChI
InChI=1S/C9H10Cl2N4/c10-6-3-5(12)4-7(11)8(6)15-9-13-1-2-14-9/h3-4H,1-2,12H2,(H2,13,14,15)
IUPAC Name
2,6-dichloro-1-N-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine
SMILES
NC1=CC(Cl)=C(NC2=NCCN2)C(Cl)=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassHalobenzenes
Direct parentDichlorobenzenes
Alternative parentsAnilines; Primary Aromatic Amines; Aryl Chlorides; Guanidines; Polyamines; Organochlorides
Substituentsaniline; aryl chloride; primary aromatic amine; aryl halide; guanidine; polyamine; organochloride; organohalogen; amine; primary amine; organonitrogen compound
Classification descriptionThis compound belongs to the dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
Pharmacology
IndicationFor prevention or reduction of intraoperative and postoperative increases in intraocular pressure (IOP) before and after ocular laser surgery when used prophylactically. Also used as a short-term adjunctive therapy in patients with open-angle glaucoma who are on maximally tolerated medical therapy requiring additional IOP reduction.
PharmacodynamicsApraclonidine significantly lowers intraocular pressure with minimal effects on cardiovascular and pulmonary parameters. It lowers intraocular pressure by reducing aqueous humor production and increasing uveoscleral outflow.
Mechanism of actionApraclonidine is a relatively selective alpha2 adrenergic receptor agonist that stimulates alpha1 receptors to a lesser extent. It has a peak ocular hypotensive effect occurring at two hours post-dosing. The exact mechanism of action is unknown, but fluorophotometric studies in animals and humans suggest that Apraclonidine has a dual mechanism of action by reducing aqueous humor production through the constriction of afferent ciliary process vessels, and increasing uveoscleral outflow.
AbsorptionTopical use of apraclonidine ophthalmic solution leads to systemic absorption. Studies of apraclonidine (0.5% ophthalmic solution) dosed one drop three times a day in both eyes for 10 days in normal volunteers yielded mean peak and trough concentrations of 0.9 ng/mL and 0.5 ng/mL, respectively.
Volume of distributionNot Available
Protein binding98.7%
Metabolism
Route of eliminationNot Available
Half life8 hours
ClearanceNot Available
ToxicityAccidental or intentional ingestion of oral apraclonidine has been reported to cause apnea, arrhythmias, asthenia, bradycardia, conduction defects, diminished or absent reflexes, dryness of the mouth, hypotension, hypothermia, hypoventilation, irritability, lethargy, miosis, pallor, respiratory depression, sedation or coma, seizure, somnolence, transient hypertension, and vomiting.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9685
Blood Brain Barrier + 0.9398
Caco-2 permeable + 0.8503
P-glycoprotein substrate Substrate 0.625
P-glycoprotein inhibitor I Non-inhibitor 0.9406
P-glycoprotein inhibitor II Non-inhibitor 0.9142
Renal organic cation transporter Inhibitor 0.7327
CYP450 2C9 substrate Non-substrate 0.8621
CYP450 2D6 substrate Non-substrate 0.7005
CYP450 3A4 substrate Non-substrate 0.6636
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.7046
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8713
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8947
Ames test Non AMES toxic 0.8937
Carcinogenicity Non-carcinogens 0.9263
Biodegradation Not ready biodegradable 0.9954
Rat acute toxicity 3.4656 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8192
hERG inhibition (predictor II) Non-inhibitor 0.891
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Alcon laboratories inc
Packagers
Dosage forms
FormRouteStrength
LiquidOphthalmic
Solution / dropsOphthalmic
Prices
Unit descriptionCostUnit
Iopidine 0.5% Solution 10ml Bottle196.37USDbottle
Iopidine 0.5% Solution 5ml Bottle98.84USDbottle
Iopidine 1 Box = 24 Packets Plastic Container16.44USDplastic
Iopidine 1% eye drops15.81USDeach
Iopidine 0.5 % Solution4.79USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States52121961993-05-182010-05-18
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.409ALOGPS
logP2.14ALOGPS
logP1.66ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)8.48ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area62.44 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity63.79 m3·mol-1ChemAxon
Polarizability23.27 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Chen PL, Chen JT, Lu DW, Chen YC, Hsiao CH: Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of horner syndrome in pediatric patients. J Ocul Pharmacol Ther. 2006 Jun;22(3):182-7. Pubmed
  2. Aslanides M, Tsiklis NS, Ozkilic E, Coskunseven E, Pallikaris G, Jankov MR: The effect of topical apraclonidine on subconjunctival hemorrhage and flap adherence in LASIK patients. J Refract Surg. 2006 Jun;22(6):585-8. Pubmed
  3. Koc F, Kansu T, Kavuncu S, Firat E: Topical apraclonidine testing discloses pupillary sympathetic denervation in diabetic patients. J Neuroophthalmol. 2006 Mar;26(1):25-9. Pubmed
  4. Garibaldi DC, Hindman HB, Grant MP, Iliff NT, Merbs SL: Effect of 0.5% apraclonidine on ptosis in Horner syndrome. Ophthal Plast Reconstr Surg. 2006 Jan-Feb;22(1):53-5. Pubmed
  5. Onal S, Gozum N, Gucukoglu A: Effect of apraclonidine versus dorzolamide on intraocular pressure after phacoemulsification. Ophthalmic Surg Lasers Imaging. 2005 Nov-Dec;36(6):457-62. Pubmed
  6. Costa VP, Harris A, Stefansson E, Flammer J, Krieglstein GK, Orzalesi N, Heijl A, Renard JP, Serra LM: The effects of antiglaucoma and systemic medications on ocular blood flow. Prog Retin Eye Res. 2003 Nov;22(6):769-805. Pubmed
External Links
ResourceLink
KEGG CompoundC07668
PubChem Compound2216
PubChem Substance46505614
ChemSpider2130
BindingDB50021812
ChEBI2788
ChEMBLCHEMBL647
Therapeutic Targets DatabaseDAP000236
PharmGKBPA164748866
Drug Product Database2076306
RxListhttp://www.rxlist.com/cgi/generic2/apraclonidine.htm
Drugs.comhttp://www.drugs.com/cdi/apraclonidine-drops.html
WikipediaApraclonidine
ATC CodesNot Available
AHFS Codes
  • 52:92.00
PDB EntriesNot Available
FDA labelshow(119 KB)
MSDSshow(57.1 KB)
Interactions
Drug Interactions
Drug
TranylcypromineThe MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha2-agonist, Apraclonidine. Concomitant therapy is contraindicated.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food InteractionsNot Available

Targets

1. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. 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. Pubmed
  4. Moodley AA, Spooner RB: Apraclonidine in the diagnosis of Horner’s syndrome. S Afr Med J. 2007 Jul;97(7):506-7. Pubmed
  5. Mirzai H, Baser EF: Congenital Horner’s syndrome and the usefulness of the apraclonidine test in its diagnosis. Indian J Ophthalmol. 2006 Sep;54(3):197-9. Pubmed
  6. New topical drugs for open-angle glaucoma. Drug Ther Bull. 2003 Feb;41(2):12-4. Pubmed
  7. Costa VP, Harris A, Stefansson E, Flammer J, Krieglstein GK, Orzalesi N, Heijl A, Renard JP, Serra LM: The effects of antiglaucoma and systemic medications on ocular blood flow. Prog Retin Eye Res. 2003 Nov;22(6):769-805. Pubmed
  8. Scheinfeld N: The use of apraclonidine eyedrops to treat ptosis after the administration of botulinum toxin to the upper face. Dermatol Online J. 2005 Mar 1;11(1):9. Pubmed
  9. Sueke H, Chandna A: Using apraclonidine in diagnosing Horner syndrome in children. Am J Ophthalmol. 2010 May;149(5):869; author reply 870. Pubmed
  10. Watts P, Satterfield D, Lim MK: Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants. J AAPOS. 2007 Jun;11(3):282-3. Pubmed
  11. Chen PL, Hsiao CH, Chen JT, Lu DW, Chen WY: Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination. Am J Ophthalmol. 2006 Sep;142(3):469-74. Pubmed

2. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

References:

  1. Moodley AA, Spooner RB: Apraclonidine in the diagnosis of Horner’s syndrome. S Afr Med J. 2007 Jul;97(7):506-7. Pubmed
  2. Mirzai H, Baser EF: Congenital Horner’s syndrome and the usefulness of the apraclonidine test in its diagnosis. Indian J Ophthalmol. 2006 Sep;54(3):197-9. Pubmed
  3. Sueke H, Chandna A: Using apraclonidine in diagnosing Horner syndrome in children. Am J Ophthalmol. 2010 May;149(5):869; author reply 870. Pubmed
  4. Kawasaki A, Borruat FX: False negative apraclonidine test in two patients with Horner syndrome. Klin Monbl Augenheilkd. 2008 May;225(5):520-2. Pubmed
  5. Watts P, Satterfield D, Lim MK: Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants. J AAPOS. 2007 Jun;11(3):282-3. Pubmed
  6. Chen PL, Hsiao CH, Chen JT, Lu DW, Chen WY: Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination. Am J Ophthalmol. 2006 Sep;142(3):469-74. Pubmed
  7. Freedman KA, Brown SM: Topical apraclonidine in the diagnosis of suspected Horner syndrome. J Neuroophthalmol. 2005 Jun;25(2):83-5. Pubmed

3. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

References:

  1. Liu JH, Dacus AC, Bartels SP: Adrenergic mechanism in circadian elevation of intraocular pressure in rabbits. Invest Ophthalmol Vis Sci. 1991 Jul;32(8):2178-83. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12