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Details

Stereochemistry ACHIRAL
Molecular Formula C9H9Cl2N3.ClH
Molecular Weight 266.555
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Clonidine hydrochloride

SMILES

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

InChI

InChIKey=ZNIFSRGNXRYGHF-UHFFFAOYSA-N
InChI=1S/C9H9Cl2N3.ClH/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9;/h1-3H,4-5H2,(H2,12,13,14);1H

HIDE SMILES / InChI

Description
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Primary
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
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
443 pg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
7313 pg × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.57 h
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

Overview

Drug as perpetrator​Drug as victim

Drug as victim

Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Blockade by agmatine of catecholamine release from chromaffin cells is unrelated to imidazoline receptors.
2001-04-06
Evidence for functional presynaptic alpha-2 adrenoceptors and their down-regulation in human heart failure.
2001-04
Oops--wrong dose of epidural clonidine in children!
2001-04
Alpha2 adrenergic receptors and the central control of breathing in the cane toad, Bufo marinus.
2001-04
Alpha2A-adrenoceptor mediated tachypnea in awake goats.
2001-04
Brain alpha(2)-adrenoceptors in monoamine-depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA.
2001-04
Sodium-induced rise in blood pressure is suppressed by androgen receptor blockade.
2001-04
[Adiuvants in the axillary brachial plexus blockade. Comparison between clonidine, sufentanil and tramadol].
2001-03-30
Alpha-adrenergic agonists inhibit the dipsogenic effect of angiotensin II by their stimulation of atrial natriuretic peptide release.
2001-03-23
Gelatin microspheres crosslinked with D,L-glyceraldehyde as a potential drug delivery system: preparation, characterisation, in vitro and in vivo studies.
2001-03-14
Morphine and clonidine activate different K+ channels on rat amygdala neurons.
2001-03-09
Linkage study of the alpha2A adrenergic receptor in attention-deficit hyperactivity disorder families.
2001-03-08
Premedication modifies the quality of sedation with propofol during regional anesthesia.
2001-03
Clonidine-induced antinociception and locomotor hypoactivity are reduced by dexamethasone in mice.
2001-03
Noradrenergic modulation of calcium currents and synaptic transmission in the olfactory bulb of Xenopus laevis tadpoles.
2001-03
Inositolphosphate formation in thoracic and abdominal rat aorta following Gq/11-coupled receptor stimulation.
2001-03
Selective imidazoline I2 ligands do not show antidepressant-like activity in the forced swim test in mice.
2001-03
Ultrasonic vocalizations of preweanling rats: involvement of both alpha(2)-adrenoceptor and kappa-opioid receptor systems.
2001-03
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.
2001-03
The antinociceptive effect of intrathecal administration of epibatidine with clonidine or neostigmine in the formalin test in rats.
2001-03
Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: an isobolographic analysis.
2001-03
The analgesic interaction between intrathecal clonidine and glutamate receptor antagonists on thermal and formalin-induced pain in rats.
2001-03
Neural circuits regulating pulsatile luteinizing hormone release in the female guinea-pig: opioid, adrenergic and serotonergic interactions.
2001-03
Noradrenergic dysfunction in the prefrontal cortex in depression: an [15O] H2O PET study of the neuromodulatory effects of clonidine.
2001-02-15
Continuous intrathecal morphine treatment for chronic pain of nonmalignant etiology: long-term benefits and efficacy.
2001-02
The impact of glycaemic control on autoregulation of glomerular filtration rate in patients with non-insulin dependent diabetes.
2001-02
Some behavioural effects of antidepressant drugs are time-dependent.
2001-02
Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial.
2001-02
Interactions of ligands at angiotensin II-receptors and imidazoline receptors.
2001-02
Imidazolines inhibit secretory responses of rat colonic mucosa to calcium-dependent but not cyclic AMP-dependent secretagogues.
2001-02
Comparison of the effects of clonidine and hydroxyzine on haemodynamic and catecholamine reactions to microlaryngoscopy.
2001-02
The use of baclofen in cluster headache.
2001-02
Differential effects of clonidine, dopamine, dobutamine, and dopexamine on basal and acid-stimulated mucosal blood flow in the rat stomach.
2001-02
[Preliminary report: the efficacy of clonidine hydrochloride ointment for postherpetic neuralgia].
2001-02
Nitric oxide and central antihypertensive drugs: one more difference between catecholamines and imidazolines.
2001-02
Mortality after coronary artery occlusion in different models of cardiac hypertrophy in rats.
2001-02
Characterization of adenylyl cyclases in cultured human granulosa cells.
2001-02
Galanin/alpha2-adrenoceptor interactions in telencephalic and diencephalic regions of the rat.
2001-01-22
Characterization of prejunctional purinoceptors inhibiting noradrenaline release in rat mesenteric arteries.
2001-01
[Cardiovascular stress protection following anesthesia induction. Comparison of clonidine and esmolol].
2001-01
Do infant rats cry?
2001-01
Antagonistic effects of selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery.
2001-01
Treatment of chronic hypertension with intravenous enalaprilat and transdermal clonidine.
2001-01
Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus: studies on the role of presynaptic alpha2-adrenoceptors.
2001-01
Drug treatment options for irritable bowel syndrome: managing for success.
2001
Alpha2 adrenergic agonists for the management of opioid withdrawal.
2001
Hypoxic-ischaemic brain damage in immature rats: effects of adrenoceptor modulation.
2001
[Potentiation of local anesthesia in endonasal surgery].
2001
P75-expressing elements are necessary for anti-allodynic effects of spinal clonidine and neostigmine.
2001
Letter: Dementia associated with clonidine therapy.
1975-03-15
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018891s028lbl.pdf
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
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.
Name Type Language
Clorpres component clonidine hydrochloride
Preferred Name English
Clonidine hydrochloride
EP   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
2-[(2,6-Dichlorophenyl)imino]imidazolidine monohydrochloride
Systematic Name English
KAPVAY
Brand Name English
Clonidine hydrochloride [JAN]
Common Name English
Clonidine hydrochloride [USAN]
Common Name English
Benzenamine, 2,6-dichloro-n-2-imidazolidinylidene-, monohydrochloride
Systematic Name English
Clonidine hydrochloride [USP-RS]
Common Name English
1H-Imidazol-2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro-, hydrochloride (1:1)
Systematic Name English
Clonidine hydrochloride [VANDF]
Common Name English
JENLOGA
Brand Name English
Clonidine hydrochloride [WHO-DD]
Common Name English
Clonidine hydrochloride [MI]
Common Name English
Clonidine hydrochloride [EP IMPURITY]
Common Name English
Onyda XR
Brand Name English
Combipres component clonidine hydrochloride
Common Name English
ST-155
Code English
Clonidine hydrochloride [MART.]
Common Name English
Clonidine hydrochloride [USP MONOGRAPH]
Common Name English
Clonidine hydrochloride [EP MONOGRAPH]
Common Name English
Clonidine hydrochloride [ORANGE BOOK]
Common Name English
DURACLON
Brand Name English
2-[(2,6-Dichlorophenyl)amino]-2-imidazoline monohydrochloride
Systematic Name English
Clonidine HCL
Common Name English
NSC-756699
Code English
Classification Tree Code System Code
NCI_THESAURUS C29709
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
EU-Orphan Drug EU/3/11/919
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
Code System Code Type Description
FDA UNII
W76I6XXF06
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
ChEMBL
CHEMBL134
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
DRUG BANK
DBSALT000538
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
EVMPD
SUB01362MIG
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
ECHA (EC/EINECS)
224-121-5
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
CAS
4205-91-8
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
RXCUI
142432
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY RxNorm
NSC
756699
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
PUBCHEM
20179
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
NCI_THESAURUS
C47979
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
SMS_ID
100000090325
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PRIMARY
MERCK INDEX
m3650
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY Merck Index
EPA CompTox
DTXSID8044670
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
DAILYMED
W76I6XXF06
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY
RS_ITEM_NUM
1140407
Created by admin on Mon Mar 31 17:47:58 GMT 2025 , Edited by admin on Mon Mar 31 17:47:58 GMT 2025
PRIMARY