Clonidine (T3D2829)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (7)XML
Targets (7)
Record Information
Version2.0
Creation Date2009-07-21 20:27:11 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2829
Identification
Common NameClonidine
ClassSmall Molecule
DescriptionClonidine, an imidazoline-derivative hypotensive agent is a centrally-acting α2-adrenergic agonist. It crosses the blood-brain barrier and acts in the hypothalamus to induce a decrease in blood pressure. It may also be administered as an epidural infusion as an adjunct treatment in the management of severe cancer pain that is not relieved by opiate analgesics alone. Clonidine may be used for differential diagnosis of pheochromocytoma in hypertensive patients. Other uses for clonidine include prophylaxis of vascular migraine headaches, treatment of severe dysmenorrhea, management of vasomotor symptoms associated with menopause, rapid detoxification in the management of opiate withdrawal, treatment of alcohol withdrawal used in conjunction with benzodiazepines, management of nicotine dependence, topical use to reduce intraocular pressure in the treatment of open-angle and secondary glaucoma and hemorrhagic glaucoma associated with hypertension, and in the treatment of attention-deficit hyperactivity disorder (ADHD). Clonidine also exhibits some peripheral activity.
Compound Type
  • Adrenergic alpha-2 Receptor Agonist
  • Adrenergic alpha-Agonist
  • Amide
  • Amine
  • Analgesic
  • Antihypertensive Agent
  • Central alpha-Agonist
  • Drug
  • Metabolite
  • Organic Compound
  • Organochloride
  • Sympatholytic
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
2,6-Dichloro-N-2-imidazolidinylidenebenzenamine
2-[(2,6-Dichlorophenyl)imino]imidazoline
Catapres
Catapres-TTS
Catapresan
Catapressan
Chlofazoline
Chlornidinum
Clonidin
Clonidina
Clonidinhydrochlorid
Clonidinum
Dixarit
Duraclon
Isoglaucon
Kapvay
Nexiclon
Run Rui
ST 155BS
Velaril
Winpress
Chemical FormulaC9H9Cl2N3
Average Molecular Mass230.094 g/mol
Monoisotopic Mass229.017 g/mol
CAS Registry Number4205-90-7
IUPAC NameN-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine
Traditional Nameclonidine
SMILESClC1=CC=CC(Cl)=C1NC1=NCCN1
InChI IdentifierInChI=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)
InChI KeyInChIKey=GJSURZIOUXUGAL-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dichlorobenzenes. Dichlorobenzenes are compounds containing a benzene with exactly two chlorine atoms attached to it.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassHalobenzenes
Direct ParentDichlorobenzenes
Alternative Parents
Substituents
  • 1,3-dichlorobenzene
  • Aniline or substituted anilines
  • Aryl chloride
  • Aryl halide
  • 2-imidazoline
  • Guanidine
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Azacycle
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point305°C
Boiling PointNot Available
SolubilityAppreciable
LogP1.59
Predicted Properties
PropertyValueSource
Water Solubility0.48 g/LALOGPS
logP2.55ALOGPS
logP2.49ChemAxon
logS-2.7ALOGPS
pKa (Strongest Basic)8.16ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area36.42 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity59.09 m³·mol⁻¹ChemAxon
Polarizability21.7 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-02vi-8910000000-a3e51d12bf5d7c152fa82017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03dl-0279000000-5f6a2e746dea4ac429522017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-0090000000-2c051509a637beaafe732017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-0090000000-f1477af875c25c537ccb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-0090000000-ccdeb1dfce0424b12c0c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-01po-6950000000-dd68628a46215027ef292017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0006-6900000000-ce531320f1fda74d127e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-03fr-2980000000-24b18e2a89a65b2b178f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001i-0190000000-7cbbf9fb244993abe9222017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-001i-0090000000-285a93c6077b8174b42b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-001i-0090000000-2fa5eb2717a38b5ddc532021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-001i-0090000000-fff41c3a9a890a8402d52021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-001i-3190000000-a3308b4d4c0c2eaa7e1e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-03l0-0920000000-7827fba3068267e11fd72021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-05gi-0900000000-7e2ad60d7fd425ea536c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-03l0-0920000000-31421af1384e151ca8042021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-1090000000-9444e2a6ad340b2e0c4e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-2190000000-b31dc3277959bc7da1f32016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-015c-9000000000-8f9953cf5ba876f810b12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0190000000-1c3f1ad6c77da1103c662016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-1590000000-be2bbba9747b473934502016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-057i-6900000000-50e611f207ee7d674aac2016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0090000000-f2dc8cf311bd04067c452021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0090000000-f2dc8cf311bd04067c452021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9410000000-64bf1288d1fd79f1dd332021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0090000000-939fc90511af10b4320a2021-09-24View Spectrum
MSMass Spectrum (Electron Ionization)splash10-003r-5970000000-33c27878b8b7ad9d5d752014-09-20View Spectrum
Toxicity Profile
Route of ExposureWell absorbed following oral administration. Bioavailability following chronic administration is approximately 65%.
Mechanism of ToxicityClonidine acts as an agonist at presynaptic alpha(2)-receptors in the nucleus tractus solitarius of the medulla oblongata. Stimulation of these receptors results in the supression of efferent sympathetic pathways and the subsequent decrease in blood pressure and vascular tone in the heart, kidneys, and peripheral vasculature. Clonidine is also a partial agonist at presynaptic alpha(2)-adrenergic receptors of peripheral nerves in vascular smooth muscle.
MetabolismHepatic. Metabolized via minor pathways. The major metabolite, p-hydroxyclonidine, is present in concentrations less than 10% of those of unchanged clonidine in urine. Four metabolites have been detected, but only p-hydroxyclonidine has been identified. Half Life: 6-20 hours; 40-60% is excreted in urine unchanged, 20% is excreted in feces. Less than 10% is excreted by p-hydroxyclonidine.
Toxicity ValuesLD50: 150 mg/kg (oral, rat) LD50: 30 mg/kg (oral, dog)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesMay be used as an adjunct in the treatment of hypertension, as an epidural infusion as an adjunct treatment in the management of severe cancer pain that is not relieved by opiate analgesics alone, for differential diagnosis of pheochromocytoma in hypertensive patients, prophylaxis of vascular migraine headaches, treatment of severe dysmenorrhea, management of vasomotor symptoms associated with menopause, rapid detoxification in the management of opiate withdrawal, treatment of alcohol withdrawal used in conjunction with benzodiazepines, management of nicotine dependence, topical use to reduce intraocular pressure in the treatment of open-angle and secondary glaucoma and hemorrhagic glaucoma associated with hypertension, and in the treatment of attention-deficit hyperactivity disorder (ADHD).
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness.
TreatmentThere is no specific antidote for clonidine overdosage. Clonidine overdosage may result in the rapid development of CNS depression; therefore, induction of vomiting with ipecac syrup is not recommended. Gastric lavage may be indicated following recent and/or large ingestions. Administration of activated charcoal and/or a cathartic may be beneficial. Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension and vasodilators for hypertension. Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension and/or coma; blood pressure should be monitored since the administration of naloxone has occasionally resulted in paradoxical hypertension. Tolazoline administration has yielded inconsistent results and is not recommended as first-line therapy. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00575
HMDB IDHMDB14714
PubChem Compound ID2803
ChEMBL IDCHEMBL134
ChemSpider ID2701
KEGG IDC07668
UniProt IDNot Available
OMIM ID
ChEBI ID46631
BioCyc IDNot Available
CTD IDNot Available
Stitch IDClonidine
PDB IDCLU
ACToR IDNot Available
Wikipedia LinkClonidine
References
Synthesis Reference

David R. Pierce, William D. Dean, Michael E. Deason, “Process for preparation of clonidine derivatives.” U.S. Patent US5684156, issued October, 1968.

MSDSLink
General References
  1. Schapiro NA: "Dude, you don't have Tourette's:" Tourette's syndrome, beyond the tics. Pediatr Nurs. 2002 May-Jun;28(3):243-6, 249-53. [12087644 ]
  2. Hossmann V, Maling TJ, Hamilton CA, Reid JL, Dollery CT: Sedative and cardiovascular effects of clonidine and nitrazepam. Clin Pharmacol Ther. 1980 Aug;28(2):167-76. [7398184 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Alpha-2A adrenergic receptor
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
References
  1. Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6. [14757140 ]
  2. Fairbanks CA, Stone LS, Kitto KF, Nguyen HO, Posthumus IJ, Wilcox GL: alpha(2C)-Adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy. J Pharmacol Exp Ther. 2002 Jan;300(1):282-90. [11752127 ]
  3. Wang XM, Zhang ZJ, Bains R, Mokha SS: Effect of antisense knock-down of alpha(2a)- and alpha(2c)-adrenoceptors on the antinociceptive action of clonidine on trigeminal nociception in the rat. Pain. 2002 Jul;98(1-2):27-35. [12098614 ]
  4. Lavand'homme PM, Ma W, De Kock M, Eisenach JC: Perineural alpha(2A)-adrenoceptor activation inhibits spinal cord neuroplasticity and tactile allodynia after nerve injury. Anesthesiology. 2002 Oct;97(4):972-80. [12357167 ]
  5. Ozdogan UK, Lahdesmaki J, Hakala K, Scheinin M: The involvement of alpha 2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice. Eur J Pharmacol. 2004 Aug 23;497(2):161-71. [15306201 ]
  6. Zhu QM, Lesnick JD, Jasper JR, MacLennan SJ, Dillon MP, Eglen RM, Blue DR Jr: Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice. Br J Pharmacol. 1999 Mar;126(6):1522-30. [10217548 ]
Target Details
2. Alpha-2B adrenergic receptor
General Function:
Epinephrine binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Zhu QM, Lesnick JD, Jasper JR, MacLennan SJ, Dillon MP, Eglen RM, Blue DR Jr: Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice. Br J Pharmacol. 1999 Mar;126(6):1522-30. [10217548 ]
Target Details
3. Alpha-2C adrenergic receptor
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular Weight:
49521.585 Da
References
  1. Zhu QM, Lesnick JD, Jasper JR, MacLennan SJ, Dillon MP, Eglen RM, Blue DR Jr: Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice. Br J Pharmacol. 1999 Mar;126(6):1522-30. [10217548 ]
Target Details
4. Substance-K receptor
General Function:
Tachykinin receptor activity
Specific Function:
This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P.
Gene Name:
TACR2
Uniprot ID:
P21452
Molecular Weight:
44441.705 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
5. Alpha-1A adrenergic receptor
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
Target Details
6. Alpha-1B adrenergic receptor
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
Target Details
7. Alpha-1D adrenergic receptor
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular Weight:
60462.205 Da