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

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
Reversal of intraocular pressure increases with 0.5% apraclonidine after dilated fundus examination in patients with chronic open-angle glaucoma.	1999 Apr	10457699
Immediate diode laser peripheral iridoplasty as treatment of acute attack of primary angle closure glaucoma: a preliminary study.	2001 Apr	11316102
Contact dermatitis to topical drugs for glaucoma.	2001 Dec	11753897
Effectiveness of apraclonidine 1% in preventing intraocular pressure rise following macular hole surgery.	2001 Feb	11159479
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
Cutaneous drug reaction case reports: from the world literature.	2002	11978142
Effects of topical antiglaucoma eye drops on prostaglandin E(2)-induced aqueous flare elevation in pigmented rabbits.	2002 Apr	11923258
Preventing intraocular pressure increase after phacoemulsification and the role of perioperative apraclonidine.	2002 Dec	12498856
Advances in topical glaucoma therapy.	2002 Mar	11940242
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
Medical therapy cost considerations for glaucoma.	2003 Jul	12834665
The effect of topical glaucoma medications evaluated by perimetry.	2003 Jun	12770987
Apraclonidine and LASIK.	2005 Dec	16325717
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
Effect of apraclonidine versus dorzolamide on intraocular pressure after phacoemulsification.	2005 Nov-Dec	16355950
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
Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination.	2006 Sep	16935593
Adverse effects of apraclonidine used in the diagnosis of Horner syndrome in infants.	2007 Jun	17572343
Pharmacologic reversal of Horner's syndrome-related ptosis with apraclonidine.	2007 May	17580803
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
Use of 0.5% apraclonidine solution in evaluation of blepharoptosis.	2008 Jul-Aug	18645436
Effects of central corneal thickness on the efficacy of topical ocular hypotensive medications.	2008 Mar	18344753
Pupillary autonomic neuropathy simulating partial Horner syndrome in diabetes mellitus and its reversal with control of blood glucose.	2008 Sep	18769297
Positive apraclonidine test within two weeks of onset of Horner syndrome caused by carotid artery dissection.	2008 Sep	18769292
[Efficacy of topic ocular hipotensive agents after posterior capsulotomy].	2008 Sep-Oct	19039468
Topical apraclonidine to diagnose Bernard-Horner syndrome.	2009	19927485
Possible effect of systemic sympathicolytic drugs on apraclonidine test.	2009 Aug	19606173
[Unilateral allergic contact dermatitis of the eyelid caused by Iopimax].	2009 Dec	20038377
Nd: YAG capsulotomy for posterior capsule opacification after combined clear corneal phacoemulsification and vitrectomy.	2009 Feb	19436607
Exposure to topical apraclonidine in children with glaucoma.	2009 Jun-Jul	19525731

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.

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