APRACLONIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H10Cl2N4
Molecular Weight	245.109
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=CC(Cl)=C(NC2=NCCN2)C(Cl)=C1

InChI

InChIKey=IEJXVRYNEISIKR-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C9H10Cl2N4
Molecular Weight	245.109
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19779s018,019lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/ppa/apraclonidine.html | https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dc7d3a9f-c0b9-411c-9c62-0a14f1718b00

Apraclonidine (IOPIDINE) is an α2-adrenergic receptor agonist and a weak α1-adrenergic receptor agonist. It is used for the prevention and treatment of postsurgical intraocular pressure elevation. The following adverse events, occurring in less than 2% of patients, were reported in association with the use of IOPIDINE Ophthalmic Solution in laser surgery: ocular injection, upper lid elevation, irregular heart rate, nasal decongestion, ocular inflammation, conjunctival blanching, and mydriasis. Interactions with other agents have not been investigated.

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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19779s018,019lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/6246501 \| https://www.ncbi.nlm.nih.gov/pubmed/11481271	Agonist 2637
Adrenergic receptor alpha-1 167 Target ID: CHEMBL2094251 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19779s018,019lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/6246501	Agonist 2637

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ocular hypertension 49 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19779s018,019lbl.pdf	Preventing		Approved 8307	IOPIDINE Approved Use Apraclonidine hydrochloride ophthalmic solution) is indicated to control or prevent postsurgical elevations in intraocular pressure that occur in patients after argon laser trabeculplasty, argon laser iridotomy or Nd:YAG posterior capsulotomy. Launch Date 5.6782081E11

C_max

Value	Dose	Co-administered	Analyte	Population
0.9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	1 drop 3 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		APRACLONIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	1 drop 3 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		APRACLONIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
74.5% DRUG LABEL https://www.google.ru/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiUl-C6ho7sAhWj_CoKHXPHBYkQFjAYegQIHBAB&url=http%3A%2F%2Fwww.ask.novartispharma.ca%2Fdownload.htm%3Fres%3Diopidine_scrip_e.pdf%26resTitleId%3D1430&usg=AOvVaw2NI2gLoHBJh4I8Nn1NkVE2	unknown, topical		APRACLONIDINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.5 % 2 times / day multiple, ophthalmic Recommended Dose: 0.5 %, 2 times / day Route: ophthalmic Route: multiple Dose: 0.5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: intraocular pressure Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	Disc. AE: Allergic reaction... AEs leading to discontinuation/dose reduction: Allergic reaction (12.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf

AEs

AE	Significance	Dose	Population
Allergic reaction	12.9% Disc. AE	0.5 % 2 times / day multiple, ophthalmic Recommended Dose: 0.5 %, 2 times / day Route: ophthalmic Route: multiple Dose: 0.5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: intraocular pressure Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020258s026lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 252

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 252	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/9305586/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2788	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2788
ZINC	ZINC000000020231	http://zinc15.docking.org/substances/ZINC000000020231

PubMed

Title	Date	PubMed
Reformulation and drop size of apraclonidine hydrochloride.	1992 Feb 15	1347973
[Glaucoma as primary optic neuropathy].	2001	12035602
[Iopidine in the control of intraocular pressure after glaucoma laser treatment].	2001	12035597
Effects of acute topical administration of clonidine 0.125%, apraclonidine 1.0% and brimonidine 0.2% on visual field parameters and ocular perfusion pressure in patients with primary open-angle glaucoma.	2002	12390124
Preventing intraocular pressure increase after phacoemulsification and the role of perioperative apraclonidine.	2002 Dec	12498856
Dorzolamide X apraclonidine in the prevention of the intraocular pressure spike after Nd : YAG laser posterior capsulotomy.	2002 Oct	12658557
The utility of 0.5% apraclonidine in the diagnosis of horner syndrome.	2003 Aug	12912704
New topical drugs for open-angle glaucoma.	2003 Feb	12630335
Ocular perfusion pressure and visual field indice modifications induced by alpha-agonist compound (clonidine 0.125%, apraclonidine 1.0% and brimonidine 0.2%) topical administration. An acute study on primary open-angle glaucoma patients.	2003 Jan-Feb	12566871
Medical therapy cost considerations for glaucoma.	2003 Jul	12834665
The effect of topical glaucoma medications evaluated by perimetry.	2003 Jun	12770987
Vitreal pathogenic role in optic pit foveolar retinoschisis and central serous retinopathy.	2003 Nov	14632616
The effects of antiglaucoma and systemic medications on ocular blood flow.	2003 Nov	14575724
Intraocular pressure spike after YAG iridotomy in patients with pigment dispersion.	2004 Apr	15180139
The use of apraclonidine in the diagnosis of horner syndrome in pediatric patients.	2004 Feb	14769608
Managing adverse events associated with botulinum toxin type A: a focus on cosmetic procedures.	2005	15943491
The utility of 0.5% apraclonidine in the diagnosis of horner syndrome.	2005 Apr	15824244
Topical apraclonidine in the diagnosis of suspected Horner syndrome.	2005 Jun	15937427
Are we ready to replace cocaine with apraclonidine in the pharmacologic diagnosis of Horner syndrome?	2005 Jun	15937425
The use of apraclonidine eyedrops to treat ptosis after the administration of botulinum toxin to the upper face.	2005 Mar 1	15748550
Comparing brimonidine 0.2% to apraclonidine 1.0% in the prevention of intraocular pressure elevation and their pupillary effects following laser peripheral iridotomy.	2005 Mar-Apr	15838723
Treatment of ptosis as a complication of botulinum toxin injection.	2005 Mar-Apr	15773880
The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis.	2005 Nov	16234449
Postoperative IOP prophylaxis practice following uncomplicated cataract surgery: a UK-wide consultant survey.	2005 Oct 7	16212667
Brimonidine 0.15% versus apraclonidine 0.5% for prevention of intraocular pressure elevation after anterior segment laser surgery.	2005 Sep	16246772
[The effect of brimonidine on the pupillary reflex. A pupillographic study in healthy volunteers].	2005 Sep	15785912
Reduction of anterior-segment vascularity with preoperative topical apraclonidine 1%.	2006 Apr	16698500
Corneal thickness- and age-related biomechanical properties of the cornea measured with the ocular response analyzer.	2006 Dec	17122122
Antagonism by imidazoline-type drugs of muscarinic and other receptors in the guinea-pig ileum.	2006 Jul	16879492
Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of horner syndrome in pediatric patients.	2006 Jun	16808679
Topical apraclonidine testing discloses pupillary sympathetic denervation in diabetic patients.	2006 Mar	16518162
Brinzolamide 1% versus apraclonidine 0.5% to prevent intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy.	2006 Sep	16931262
Apraclonidine in the diagnosis of Horner's syndrome.	2007 Jul	17824139
Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants.	2007 Jun	17572343
Horner's syndrome, Pseudo-Horner's syndrome, and simple anisocoria.	2007 Sep	17764630
Medical management of primary open-angle glaucoma: Best practices associated with enhanced patient compliance and persistency.	2008 Feb 2	19920977
The role of cyclosporine and mycophenolate in an orthotopic porcine-to-rat corneal xenotransplantation.	2008 Jun	18583888
Central alpha-2 adrenergic eye drops: case series of 3 pediatric systemic poisonings.	2008 Mar	18347496
Effects of central corneal thickness on the efficacy of topical ocular hypotensive medications.	2008 Mar	18344753
Differences in the histopathology and matrix metalloproteinase expression in Tenon's tissue of primary open-angle glaucoma and primary angle-closure glaucoma.	2008 Mar	18323704
Acupuncture treatment for idiopathic Horner's syndrome in a dog.	2008 Mar	18296897
Fixed combination of topical brimonidine 0.2% and timolol 0.5% for glaucoma and uncontrolled intraocular pressure.	2008 Sep	19668752
Pupillary autonomic neuropathy simulating partial Horner syndrome in diabetes mellitus and its reversal with control of blood glucose.	2008 Sep	18769297
[Efficacy of topic ocular hipotensive agents after posterior capsulotomy].	2008 Sep-Oct	19039468
Topical apraclonidine to diagnose Bernard-Horner syndrome.	2009	19927485
Oral versus topical carbonic anhydrase inhibitors in ocular hypertension after scleral tunnel cataract surgery.	2009	19668590
[Unilateral allergic contact dermatitis of the eyelid caused by Iopimax].	2009 Dec	20038377
[Usefulness of apraclonidine in the diagnosis of Horner syndrome].	2009 Feb	19253181
False-negative apraclonidine testing in acute Horner syndrome.	2009 Feb	19169332
Ocular decompression retinopathy after trabeculectomy with mitomycin-C for angle recession glaucoma.	2009 Mar-Apr	19237794

Patents

Sample Use Guides

In Vivo Use Guide

One drop of Ophthalmic Solution should be instilled in the scheduled operative eye one hour before initiating anterior segment laser surgery and a second drop should be instilled to the same eye immediately upon completion of the laser surgical procedure. Use a separate container for each single-drop dose and discard each container after use.

Route of Administration: Topical

In Vitro Use Guide

The alpha(2)-adrenoceptor agonists apraclonidine induced vasoconstriction in the porcine ciliary artery with the potency EC(50) equal to 13.0 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 18:09:09 UTC 2022` Edited by `admin` on `Fri Dec 16 18:09:09 UTC 2022`
Record UNII	843CEN85DI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

APRACLONIDINE

Official Name

English

APRACLONIDINE [VANDF]

Common Name

English

apraclonidine [INN]

Common Name

English

APRACLONIDINE [MI]

Common Name

English

Apraclonidine [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

S01EA03