Identification

Name
Apraclonidine
Accession Number
DB00964  (APRD00012)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • 4-Aminoclonidine
  • Apraclonidina
  • Apraclonidine
  • Apraclonidinum
Product Ingredients
IngredientUNIICASInChI Key
Apraclonidine HydrochlorideD2VW67N38H73218-79-8OTQYGBJVDRBCHC-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IopidineSolution1 %OphthalmicNovartis1992-12-31Not applicableCanada
IopidineSolution / drops10 mg/1mLOphthalmicAlcon, Inc.1988-05-15Not applicableUs
IopidineSolution0.5 %OphthalmicNovartis1995-12-31Not applicableCanada
IopidineSolution5 mg/1mLOphthalmicAlcon, Inc.1993-10-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ApraclonidineSolution5.75 mg/1mLOphthalmicSandoz2009-07-19Not applicableUs
ApraclonidineSolution5.75 mg/1mLOphthalmicFALCON Pharmaceuticals, Ltd.2009-07-192011-07-29Us
Apraclonidine OphthalmicSolution / drops5 mg/1mLOphthalmicAkorn2009-08-12Not applicableUs
Categories
UNII
843CEN85DI
CAS number
66711-21-5
Weight
Average: 245.109
Monoisotopic: 244.028251754
Chemical Formula
C9H10Cl2N4
InChI Key
IEJXVRYNEISIKR-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-N1-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine
SMILES
NC1=CC(Cl)=C(NC2=NCCN2)C(Cl)=C1

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Apraclonidine 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 action

Apraclonidine 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.

TargetActionsOrganism
AAlpha-2A adrenergic receptor
agonist
Human
AAlpha-1A adrenergic receptor
agonist
Human
UAlpha-2B adrenergic receptor
agonist
Human
Absorption

Topical 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 distribution
Not Available
Protein binding

98.7%

Metabolism
Not Available
Route of elimination
Not Available
Half life

8 hours

Clearance
Not Available
Toxicity

Accidental 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
BenmoxinBenmoxin may increase the alpha-adrenergic activities of Apraclonidine.
CaroxazoneCaroxazone may increase the alpha-adrenergic activities of Apraclonidine.
ClorgilineClorgiline may increase the alpha-adrenergic activities of Apraclonidine.
FurazolidoneFurazolidone may increase the alpha-adrenergic activities of Apraclonidine.
HarmalineHarmaline may increase the alpha-adrenergic activities of Apraclonidine.
HydracarbazineHydracarbazine may increase the alpha-adrenergic activities of Apraclonidine.
IproniazidIproniazid may increase the alpha-adrenergic activities of Apraclonidine.
IsocarboxazidIsocarboxazid may increase the alpha-adrenergic activities of Apraclonidine.
LinezolidLinezolid may increase the alpha-adrenergic activities of Apraclonidine.
MebanazineMebanazine may increase the alpha-adrenergic activities of Apraclonidine.
Food Interactions
Not Available

References

General References
  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:16808679]
  2. Aslanides lM, Tsiklis NS, Ozkilic E, Coskunseven E, Pallikaris lG, 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:16805122]
  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:16518162]
  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:16418668]
  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:16355950]
  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:14575724]
External Links
Human Metabolome Database
HMDB0015099
KEGG Compound
C07668
PubChem Compound
2216
PubChem Substance
46505614
ChemSpider
2130
BindingDB
50021812
ChEBI
2788
ChEMBL
CHEMBL647
Therapeutic Targets Database
DAP000236
PharmGKB
PA164748866
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Apraclonidine
ATC Codes
S01EA03 — Apraclonidine
AHFS Codes
  • 52:92.00 — EENT Drugs, Miscellaneous
FDA label
Download (119 KB)
MSDS
Download (57.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableUnknown StatusTreatmentGlaucoma / Ocular Hypertension1

Pharmacoeconomics

Manufacturers
  • Akorn inc
  • Alcon laboratories inc
Packagers
  • Akorn Inc.
  • Alcon Laboratories
  • Dispensing Solutions
  • Falcon Pharmaceuticals Ltd.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
SolutionOphthalmic5.75 mg/1mL
Solution / dropsOphthalmic5 mg/1mL
SolutionOphthalmic0.5 %
SolutionOphthalmic1 %
SolutionOphthalmic5 mg/1mL
Solution / dropsOphthalmic10 mg/1mL
Prices
Unit descriptionCostUnit
Iopidine 0.5% Solution 10ml Bottle196.37USD bottle
Iopidine 0.5% Solution 5ml Bottle98.84USD bottle
Iopidine 1 Box = 24 Packets Plastic Container16.44USD plastic
Iopidine 1% eye drops15.81USD each
Iopidine 0.5 % Solution4.79USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5212196No1993-05-182010-05-18Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.409 mg/mLALOGPS
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
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9685
Blood Brain Barrier+0.9398
Caco-2 permeable+0.8503
P-glycoprotein substrateSubstrate0.625
P-glycoprotein inhibitor INon-inhibitor0.9406
P-glycoprotein inhibitor IINon-inhibitor0.9142
Renal organic cation transporterInhibitor0.7327
CYP450 2C9 substrateNon-substrate0.8621
CYP450 2D6 substrateNon-substrate0.7005
CYP450 3A4 substrateNon-substrate0.6636
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.7046
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8713
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8947
Ames testNon AMES toxic0.8937
CarcinogenicityNon-carcinogens0.9263
BiodegradationNot ready biodegradable0.9954
Rat acute toxicity3.4656 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8192
hERG inhibition (predictor II)Non-inhibitor0.891
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Dichlorobenzenes
Alternative Parents
Aniline and substituted anilines / Aryl chlorides / Imidazolines / Guanidines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organochlorides
show 1 more
Substituents
1,3-dichlorobenzene / Aniline or substituted anilines / Aryl chloride / Aryl halide / 2-imidazoline / Guanidine / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Carboximidamide / Azacycle
show 10 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
guanidines, dichlorobenzene, imidazolines (CHEBI:2788)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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 oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
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:17139284]
  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:17016423]
  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:11481271]
  4. Moodley AA, Spooner RB: Apraclonidine in the diagnosis of Horner's syndrome. S Afr Med J. 2007 Jul;97(7):506-7. [PubMed:17824139]
  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:16921219]
  6. Authors unspecified: New topical drugs for open-angle glaucoma. Drug Ther Bull. 2003 Feb;41(2):12-4. [PubMed:12630335]
  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:14575724]
  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:15748550]
  9. Sueke H, Chandna A: Using apraclonidine in diagnosing Horner syndrome in children. Am J Ophthalmol. 2010 May;149(5):869; author reply 870. doi: 10.1016/j.ajo.2010.01.023. [PubMed:20399934]
  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:17572343]
  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:16935593]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
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:17824139]
  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:16921219]
  3. Sueke H, Chandna A: Using apraclonidine in diagnosing Horner syndrome in children. Am J Ophthalmol. 2010 May;149(5):869; author reply 870. doi: 10.1016/j.ajo.2010.01.023. [PubMed:20399934]
  4. Kawasaki A, Borruat FX: False negative apraclonidine test in two patients with Horner syndrome. Klin Monbl Augenheilkd. 2008 May;225(5):520-2. doi: 10.1055/s-2008-1027349. [PubMed:18454417]
  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:17572343]
  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:16935593]
  7. Freedman KA, Brown SM: Topical apraclonidine in the diagnosis of suspected Horner syndrome. J Neuroophthalmol. 2005 Jun;25(2):83-5. [PubMed:15937427]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
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:1676991]

Drug created on June 13, 2005 07:24 / Updated on December 18, 2018 05:46