U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C9H9Cl2N3
Molecular Weight 230.0941
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLONIDINE

SMILES

c1cc(c(c(c1)Cl)NC2=NCCN2)Cl

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 230.0941
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: 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

466214400000
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

1254182400000
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

466214400000
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
Doses

Doses

DosePopulationAdverse events​
0.25 mg 2 times / day multiple, oral
Studied dose
Dose: 0.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.25 mg, 2 times / day
Sources:
unhealthy, 13 years
Health Status: unhealthy
Age Group: 13 years
Sex: M
Sources:
Other AEs: Suicide attempt...
2 mg 3 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 3 times / day
Route: oral
Route: multiple
Dose: 2 mg, 3 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 10 years
Health Status: unhealthy
Age Group: median age 10 years
Sex: M+F
Sources:
Disc. AE: Bradyphrenia...
AEs leading to
discontinuation/dose reduction:
Bradyphrenia (1%)
Sources:
0.1 mg 2 times / day multiple, oral
Recommended
Dose: 0.1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.1 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Disc. AE: Somnolence, Fatigue...
AEs leading to
discontinuation/dose reduction:
Somnolence (3.9%)
Fatigue (2.6%)
Sources:
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Disc. AE: Somnolence, Fatigue...
AEs leading to
discontinuation/dose reduction:
Somnolence (6.4%)
Fatigue (5.1%)
Constipation (1.3%)
Vomiting (1.3%)
Electrocardiogram QT prolonged (1.3%)
Rash (1.3%)
Sources:
0.1 mg 2 times / day steady, oral
Dose: 0.1 mg, 2 times / day
Route: oral
Route: steady
Dose: 0.1 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Other AEs: Dry mouth, Drowsiness...
Other AEs:
Dry mouth (below serious, 16 patients)
Drowsiness (below serious, 5 patients)
Lightheadedness (below serious, 6 patients)
Fatigue (below serious, 8 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Suicide attempt
0.25 mg 2 times / day multiple, oral
Studied dose
Dose: 0.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.25 mg, 2 times / day
Sources:
unhealthy, 13 years
Health Status: unhealthy
Age Group: 13 years
Sex: M
Sources:
Bradyphrenia 1%
Disc. AE
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 10 years
Health Status: unhealthy
Age Group: median age 10 years
Sex: M+F
Sources:
Fatigue 2.6%
Disc. AE
0.1 mg 2 times / day multiple, oral
Recommended
Dose: 0.1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.1 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Somnolence 3.9%
Disc. AE
0.1 mg 2 times / day multiple, oral
Recommended
Dose: 0.1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.1 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Constipation 1.3%
Disc. AE
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Electrocardiogram QT prolonged 1.3%
Disc. AE
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Rash 1.3%
Disc. AE
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Vomiting 1.3%
Disc. AE
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Fatigue 5.1%
Disc. AE
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Somnolence 6.4%
Disc. AE
0.2 mg 2 times / day multiple, oral
Recommended
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Sources:
unhealthy, median age 9 years
Health Status: unhealthy
Age Group: median age 9 years
Sex: M+F
Sources:
Dry mouth below serious, 16 patients
0.1 mg 2 times / day steady, oral
Dose: 0.1 mg, 2 times / day
Route: oral
Route: steady
Dose: 0.1 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Drowsiness below serious, 5 patients
0.1 mg 2 times / day steady, oral
Dose: 0.1 mg, 2 times / day
Route: oral
Route: steady
Dose: 0.1 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Lightheadedness below serious, 6 patients
0.1 mg 2 times / day steady, oral
Dose: 0.1 mg, 2 times / day
Route: oral
Route: steady
Dose: 0.1 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Fatigue below serious, 8 patients
0.1 mg 2 times / day steady, oral
Dose: 0.1 mg, 2 times / day
Route: oral
Route: steady
Dose: 0.1 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Overview

Overview

Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Sexual dysfunction related to antihypertensive agents: results from the animal model.
1999 Apr
Cocaine-induced hypertension: role of the peripheral sympathetic system.
1999 Aug
Scopolamine-induced convulsions in food given fasted mice: effects of clonidine and tizanidine.
1999 Jun
Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking.
2000 Aug
Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for labor analgesia.
2000 Feb
[Clonidine hallucinations: description of a clinical case].
2000 Jan-Feb
The influence of indomethacin on the acth secretion induced by central stimulation of adrenergic receptors.
2000 Jun
Hypertensive crisis and myocardial infarction following massive clonidine overdose.
2000 May
Optimal dose of intrathecal clonidine added to sufentanil plus bupivacaine for labour analgesia.
2000 Sep
P75-expressing elements are necessary for anti-allodynic effects of spinal clonidine and neostigmine.
2001
Oops--wrong dose of epidural clonidine in children!
2001 Apr
Alpha2 adrenergic receptors and the central control of breathing in the cane toad, Bufo marinus.
2001 Apr
Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial.
2001 Feb
The use of baclofen in cluster headache.
2001 Feb
Mortality after coronary artery occlusion in different models of cardiac hypertrophy in rats.
2001 Feb
Characterization of adenylyl cyclases in cultured human granulosa cells.
2001 Feb
Effectiveness of apraclonidine 1% in preventing intraocular pressure rise following macular hole surgery.
2001 Feb
Exercise attenuates alpha-adrenergic-receptor responsiveness in skeletal muscle vasculature.
2001 Jan
A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient.
2001 Jan
Use of trifluoroperazine isolates a [(3)H]Ifenprodil binding site in rat brain membranes with the pharmacology of the voltage-independent ifenprodil site on N-methyl-D-aspartate receptors containing NR2B subunits.
2001 Jan
Baclofen-impairment of memory retention in rats: possible interaction with adrenoceptor mechanism(s).
2001 Jan 12
Galanin/alpha2-adrenoceptor interactions in telencephalic and diencephalic regions of the rat.
2001 Jan 22
Clonidine-induced antinociception and locomotor hypoactivity are reduced by dexamethasone in mice.
2001 Mar
Noradrenergic modulation of calcium currents and synaptic transmission in the olfactory bulb of Xenopus laevis tadpoles.
2001 Mar
Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: an isobolographic analysis.
2001 Mar
The analgesic interaction between intrathecal clonidine and glutamate receptor antagonists on thermal and formalin-induced pain in rats.
2001 Mar
Neural circuits regulating pulsatile luteinizing hormone release in the female guinea-pig: opioid, adrenergic and serotonergic interactions.
2001 Mar
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018891s028lbl.pdf
Oral
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.
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:54:07 UTC 2021
Edited
by admin
on Fri Jun 25 20:54:07 UTC 2021
Record UNII
MN3L5RMN02
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CLONIDINE
HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
CLONIDINE [VANDF]
Common Name English
CLONIDINE [WHO-DD]
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
CATARPRES-TTS
Brand 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
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-ATC S01EA04
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
NDF-RT N0000009918
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-VATC QC02LC01
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-ATC N02CX02
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-VATC QC02LC51
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-VATC QN02CX02
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
NCI_THESAURUS C29709
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
FDA ORPHAN DRUG 425614
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
NDF-RT N0000175554
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
FDA ORPHAN DRUG 34388
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-VATC QC02AC01
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-VATC QS01EA04
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
LIVERTOX 225
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-ATC C02AC01
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
WHO-ATC C02LC01
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C380
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
EPA CompTox
4205-90-7
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
DRUG BANK
DB00575
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
RXCUI
2599
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY RxNorm
FDA UNII
MN3L5RMN02
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
CAS
4205-90-7
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
ECHA (EC/EINECS)
224-119-4
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
MESH
D003000
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
IUPHAR
516
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
PUBCHEM
2803
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
LACTMED
Clonidine
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
USP_CATALOG
1140393
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY USP-RS
INN
2624
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
WIKIPEDIA
CLONIDINE
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
ChEMBL
CHEMBL134
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
DRUG CENTRAL
704
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
MERCK INDEX
M3650
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY Merck Index
HSDB
3040
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
EVMPD
SUB06730MIG
Created by admin on Fri Jun 25 20:54:07 UTC 2021 , Edited by admin on Fri Jun 25 20:54:07 UTC 2021
PRIMARY
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