CLONIDINE

First approved in 1974

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H9Cl2N3
Molecular Weight	230.094
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC=CC(Cl)=C1NC2=NCCN2

InChI

InChIKey=GJSURZIOUXUGAL-UHFFFAOYSA-N

InChI=1S/C9H9Cl2N3/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9/h1-3H,4-5H2,(H2,12,13,14)

HIDE SMILES / InChI

Molecular Formula	C9H9Cl2N3
Molecular Weight	230.094
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/2012/018891s028lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017407s037lbl.pdf | https://clinicaltrials.gov/ct2/show/NCT02177461 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022331lbl.pdf | https://clinicaltrials.gov/ct2/show/NCT00556959

Clonidine is a centrally acting α2 adrenergic agonist and imidazoline receptor agonist used to treat high blood pressure, attention deficit hyperactivity disorder, anxiety disorders, tic disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions. Clonidine treats high blood pressure by stimulating α2 receptors in the brain, which decreases peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, thus inhibiting the release of norepinephrine (NE). It has also been proposed that the antihypertensive effect of clonidine is due to agonism on the I1 receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure. Clonidines mechanism of action in the treatment of ADHD is to increase noradrenergic tone in the prefrontal cortex (PFC) directly by binding to postsynaptic α2A adrenergic receptors and indirectly by increasing norepinephrine input from the locus coeruleus. Clonidine indicated in the treatment of hypertension. Clonidine hydrochloride tablets may be employed alone or concomitantly with other antihypertensive agents. The US Food and Drug Administration (FDA) has approved clonidine for the treatment of attention deficit hyperactivity disorder (ADHD), under the trade name of Kapvay alone or with stimulants in 2010, for pediatric patients aged 6–17 years.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Alpha-2a adrenergic receptor 70 Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27265687	Partial Agonist 297	30.2 nM [EC50]
Adrenergic receptor alpha-2 114 Target ID: CHEMBL2095158 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25521963	Partial Agonist 297	3.8 nM [Ki]
Alpha-2b adrenergic receptor 35 Target ID: CHEMBL1942 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22750139	Partial Agonist 297	31.6 nM [Ki]
Alpha-2c adrenergic receptor 44 Target ID: CHEMBL1916 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22750139	Partial Agonist 297	9.3 nM [Ki]
Adrenergic receptor alpha-1 171 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8784451	Partial Agonist 297	290.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 575 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/017407s037lbl.pdf	Primary	Approved 8583	CATAPRES-TTS-1 Approved Use INDICATIONS & USAGE Clonidine hydrochloride tablets, USP are indicated in the treatment of hypertension. Clonidine hydrochloride tablets, USP may be employed alone or concomitantly with other antihypertensive agents. Launch Date 1984
Attention deficit hyperactivity disorder 70 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022331s013lbl.pdf	Primary	Approved 8583	KAPVAY Approved Use INDICATIONS AND USAGE. KAPVAY® is a centrally acting alpha2-adrenergic agonist indicated for the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy or as adjunctive therapy to stimulant medications Launch Date 2009
Opioid withdrawal 4 Sources: https://clinicaltrials.gov/ct2/show/NCT03174067	Primary	Phase IV 63	CATAPRES-TTS-1 Approved Use INDICATIONS & USAGE Clonidine hydrochloride tablets, USP are indicated in the treatment of hypertension. Clonidine hydrochloride tablets, USP may be employed alone or concomitantly with other antihypertensive agents. Launch Date 1984

C_max

Value	Dose	Co-administered	Analyte	Population
443 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022331s021lbl.pdf	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:		CLONIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
7313 pg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022331s021lbl.pdf	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:		CLONIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.57 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022331s021lbl.pdf	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:		CLONIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 OCT1 620 L-type Ca2+ channels 28 K+ channels 73	CYP1A2 1197 CYP1A1 389 CYP3A5 446 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C18 149 CYP2C19 1119 CYP2E1 729 CYP2J2 71 CYP1B1 104

Drug as perpetrator

Target	Modality	Activity
P-gp 1932	inhibitor 4027 Sources: https://www.sciencedirect.com/science/article/abs/pii/0006291X9091939P Page: 265.0	likely
L-type Ca2+ channels 30	inhibitor 4027 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0006899300025920 Page: abstract	no
K+ channels 73	inhibitor 4027 Sources: https://journals.lww.com/anesthesia-analgesia/Fulltext/2011/12000/Molecular_Mechanisms_of_the_Inhibitory_Effects_of.14.aspx Page: abstract	yes [IC50 1.21 uM]
OCT1 656	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129651/ Page: 3.0	yes

Drug as victim

Target	Modality	Activity
CYP1B1 104	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP2A6 626	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP2B6 776	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP2C18 149	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP2C19 1119	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP2C8 810	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP2C9 1193	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP2E1 729	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP2J2 71	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: 1.0	no
CYP1A1 389	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: abstract	yes
CYP1A2 1197	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: abstract	yes
CYP2D6 1388	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: abstract	yes
CYP3A4 1946	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: abstract	yes
CYP3A5 446	substrate 4014 Sources: https://dmd.aspetjournals.org/content/38/9/1393.short Page: abstract	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.sciencedirect.com/science/article/abs/pii/S1056871907002808 Page: 102.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY554135	https://www.001chemical.com/chem/4205-90-7
Achemo Scientific Limited	AC-35091	http://www.achemo.com/product_view.asp?ID=132847
AK Scientific, Inc. (AKSCI)	M199	http://www.aksci.com/item_detail.php?cat=M199
Alfa Chemistry	4205-90-7	https://www.alfa-chemistry.com/clonidine-200-mg-cas-4205-90-7-item-291955.htm
Alfa Chemistry	AP4205907-A	https://reagents.alfa-chemistry.com/product/clonidine-solution-cas-4205-90-7-11301.html
Alfa Chemistry	AP4205907-B	https://reagents.alfa-chemistry.com/product/clonidine-cas-4205-90-7-11302.html
Aurora Fine Chemicals LLC	A12.862.925	http://online.aurorafinechemicals.com/info?ID=A12.862.925
Aurum Pharmatech LLC	H1640	http://www.Aurumpharmatech.com/Product/ProductDetails/H1640
AvaChem Scientific	1506B	http://www.avachem.com/productSearch.asp?1506B
BioChemPartner	BCP07223	http://www.biochempartner.com/4205-90-7-BCP07223
BLD Pharm	BD121967	http://www.bldpharm.com/products/4205-90-7.html
BLD Pharm	BD425824	http://www.bldpharm.com/products/54707-71-0.html
Chem Scene	CS-0012297	http://www.chemscene.com/4205-90-7.html
ChemMol	49411858	http://www.chemmol.com/chemmol/49411858.html
ChemMol	99094595	http://www.chemmol.com/chemmol/99094595.html
ChemShuttle	181502	http://www.chemshuttle.com/catalogsearch/result/?q=4205-90-7&cat=
Chemspace	CSSB00011218712	https://chem-space.com/CSSB00011218712
Clearsynth	CS-T-13180	https://www.clearsynth.com/en/CST13180.html
eNovation Chemicals	D673838	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673838
Finetech	FT-0741246	http://www.finetechnology-ind.com/prod/detail/pub/4205-90-7.html
Hairui	HR135273	http://www.hairuichem.com/en/product/4205-90-7.html
Lab Network	LN00326971	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00326971
mcule	MCULE-5017779690	https://mcule.com/MCULE-5017779690/
MedChem Express	HY-12721	https://www.medchemexpress.com/clonidine.html
Molcore	MC554135	https://www.molcore.com/product/4205-90-7
MolPort	MolPort-001-779-668	https://www.molport.com/shop/molecule-link/MolPort-001-779-668
MolPort	MolPort-005-932-374	https://www.molport.com/shop/molecule-link/MolPort-005-932-374
Parchem	28580	http://www.parchem.com/chemical-supplier-distributor/Clonidine-Hydrochloride-018580.aspx
Sigma-Aldrich	C-033_CERILLIAN	https://www.sigmaaldrich.com/catalog/product/cerillian/c033?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S524033	http://www.smolecule.com/products/s524033
Smolecule	S772548	https://www.smolecule.com/products/s772548
THE BioTek	bt-263892	https://www.thebiotek.com/product/inhibitors/bt-263892
THE BioTek	bt-291913	https://www.thebiotek.com/product/others/bt-291913

PubMed

Title	Date	PubMed
Letter: Dementia associated with clonidine therapy.	1975 Mar 15	1125640
Drug treatment options for irritable bowel syndrome: managing for success.	2001	11302287
Alpha2 adrenergic agonists for the management of opioid withdrawal.	2001	11279747
Hypoxic-ischaemic brain damage in immature rats: effects of adrenoceptor modulation.	2001	11277361
[Potentiation of local anesthesia in endonasal surgery].	2001	11247245
P75-expressing elements are necessary for anti-allodynic effects of spinal clonidine and neostigmine.	2001	11226704
Evidence for functional presynaptic alpha-2 adrenoceptors and their down-regulation in human heart failure.	2001 Apr	11300430
Oops--wrong dose of epidural clonidine in children!	2001 Apr	11300396
Alpha2 adrenergic receptors and the central control of breathing in the cane toad, Bufo marinus.	2001 Apr	11282388
Alpha2A-adrenoceptor mediated tachypnea in awake goats.	2001 Apr	11282385
Brain alpha(2)-adrenoceptors in monoamine-depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA.	2001 Apr	11264240
Sodium-induced rise in blood pressure is suppressed by androgen receptor blockade.	2001 Apr	11247793
Blockade by agmatine of catecholamine release from chromaffin cells is unrelated to imidazoline receptors.	2001 Apr 6	11301064
Continuous intrathecal morphine treatment for chronic pain of nonmalignant etiology: long-term benefits and efficacy.	2001 Feb	11301086
The impact of glycaemic control on autoregulation of glomerular filtration rate in patients with non-insulin dependent diabetes.	2001 Feb	11300610
Some behavioural effects of antidepressant drugs are time-dependent.	2001 Feb	11294483
Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial.	2001 Feb	11286609
Interactions of ligands at angiotensin II-receptors and imidazoline receptors.	2001 Feb	11286399
Imidazolines inhibit secretory responses of rat colonic mucosa to calcium-dependent but not cyclic AMP-dependent secretagogues.	2001 Feb	11273018
Comparison of the effects of clonidine and hydroxyzine on haemodynamic and catecholamine reactions to microlaryngoscopy.	2001 Feb	11270028
The use of baclofen in cluster headache.	2001 Feb	11252142
Differential effects of clonidine, dopamine, dobutamine, and dopexamine on basal and acid-stimulated mucosal blood flow in the rat stomach.	2001 Feb	11246314
[Preliminary report: the efficacy of clonidine hydrochloride ointment for postherpetic neuralgia].	2001 Feb	11244770
Nitric oxide and central antihypertensive drugs: one more difference between catecholamines and imidazolines.	2001 Feb	11230279
Mortality after coronary artery occlusion in different models of cardiac hypertrophy in rats.	2001 Feb	11230273
Characterization of adenylyl cyclases in cultured human granulosa cells.	2001 Feb	11226046
Noradrenergic dysfunction in the prefrontal cortex in depression: an [15O] H2O PET study of the neuromodulatory effects of clonidine.	2001 Feb 15	11239902
Characterization of prejunctional purinoceptors inhibiting noradrenaline release in rat mesenteric arteries.	2001 Jan	11243573
[Cardiovascular stress protection following anesthesia induction. Comparison of clonidine and esmolol].	2001 Jan	11220254
Do infant rats cry?	2001 Jan	11212634
Antagonistic effects of selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery.	2001 Jan	11206183
Treatment of chronic hypertension with intravenous enalaprilat and transdermal clonidine.	2001 Jan	11198612
Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus: studies on the role of presynaptic alpha2-adrenoceptors.	2001 Jan	11191838
Galanin/alpha2-adrenoceptor interactions in telencephalic and diencephalic regions of the rat.	2001 Jan 22	11201077
[Adiuvants in the axillary brachial plexus blockade. Comparison between clonidine, sufentanil and tramadol].	2001 Jan-Feb	11279374
Premedication modifies the quality of sedation with propofol during regional anesthesia.	2001 Mar	11305831
Clonidine-induced antinociception and locomotor hypoactivity are reduced by dexamethasone in mice.	2001 Mar	11291750
Noradrenergic modulation of calcium currents and synaptic transmission in the olfactory bulb of Xenopus laevis tadpoles.	2001 Mar	11285006
Inositolphosphate formation in thoracic and abdominal rat aorta following Gq/11-coupled receptor stimulation.	2001 Mar	11284447
Selective imidazoline I2 ligands do not show antidepressant-like activity in the forced swim test in mice.	2001 Mar	11277603
Ultrasonic vocalizations of preweanling rats: involvement of both alpha(2)-adrenoceptor and kappa-opioid receptor systems.	2001 Mar	11274995
Effects of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on alpha2-adrenoceptors which regulate the synthesis and release of noradrenaline in the rat brain.	2001 Mar	11245411
The antinociceptive effect of intrathecal administration of epibatidine with clonidine or neostigmine in the formalin test in rats.	2001 Mar	11240085
Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: an isobolographic analysis.	2001 Mar	11226110
The analgesic interaction between intrathecal clonidine and glutamate receptor antagonists on thermal and formalin-induced pain in rats.	2001 Mar	11226109
Neural circuits regulating pulsatile luteinizing hormone release in the female guinea-pig: opioid, adrenergic and serotonergic interactions.	2001 Mar	11207938
Gelatin microspheres crosslinked with D,L-glyceraldehyde as a potential drug delivery system: preparation, characterisation, in vitro and in vivo studies.	2001 Mar 14	11250103
Alpha-adrenergic agonists inhibit the dipsogenic effect of angiotensin II by their stimulation of atrial natriuretic peptide release.	2001 Mar 23	11259763
Linkage study of the alpha2A adrenergic receptor in attention-deficit hyperactivity disorder families.	2001 Mar 8	11304829
Morphine and clonidine activate different K+ channels on rat amygdala neurons.	2001 Mar 9	11245859

Patents

Sample Use Guides

In Vivo Use Guide

Oral Initial Dose 0.1 mg tablet twice daily (morning and bedtime). Elderly patients may benefit from a lower initial dose Maintenance Dose Further increments of 0.1 mg per day may be made at weekly intervals if necessary until the desired response is achieved. Taking the larger portion of the oral daily dose at bedtime may minimize transient adjustment effects of dry mouth and drowsiness. The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day given in divided doses. Studies have indicated that 2.4 mg is the maximum effective daily dose, but doses as high as this have rarely been employed. Transdermal: once every 7 days to a hairless area of intact skin on the upper outer arm or chest.

Route of Administration: Other

In Vitro Use Guide

Neural membranes (P2 fractions) were prepared from the prefrontal cortex of human brains obtained at autopsy. Specific Clonidine binding was measured in 0.55 mL aliquots (50 mM Tris HCl, pH 7.5) of the neural membranes, which were incubated with [3H]RX821002 (1 nM) for 30 min at 25 °C in the absence or presence of the Clonidine (10^-12 M to 10^-3 M, 10 concentrations). Specific binding was determined and plotted as a function of the compound concentration. Incubations were terminated by diluting the samples with 5 mL of ice-cold Tris incubation buffer (4 °C). Membrane-bound [3H]RX821002 was separated by vacuum filtration through Whatman GF/C glass fiber filters. Then the filters were rinsed twice with 5 mL of incubation buffer and transferred to minivials containing 3 mL of OptiPhase “HiSafe” II cocktail and counted for radioactivity by liquid scintillation spectrometry.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 07:41:07 GMT 2025` Edited by `admin` on `Wed Apr 02 07:41:07 GMT 2025`
Record UNII	MN3L5RMN02
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

CLONIDINE

Official Name

English

CATARPRES-TTS

Preferred Name

English

CLONIDINE [VANDF]

Common Name

English

ST-155-BS

Code

English

CLONIDINE [HSDB]

Common Name

English

CLONIDINE [USP-RS]

Common Name

English

CLONIDINE EXTENDED RELEASE

Common Name

English

CLONIDINE [MI]

Common Name

English

CLONIDINE [USAN]

Common Name

English

CLONIDINE [JAN]

Common Name

English

Clonidine [WHO-DD]

Common Name

English

CLONIDINE [MART.]

Common Name

English

CLONIDINE [ORANGE BOOK]

Common Name

English

2-[(2,6-Dichlorophenyl)imino]imidazolidine

Systematic Name

English

clonidine [INN]

Common Name

English

CLONIDINE [USP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C02LC51