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Systematic (IUPAC) name
Clinical data
Trade names Catapres, Kapvay, Nexiclon
AHFS/ monograph
MedlinePlus a682243
Licence data US FDA:link
Pregnancy cat. B3 (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes oral, epidural, IV, transdermal, topical
Pharmacokinetic data
Bioavailability 75-85% (IR), 89% (XR)[1]
Protein binding 20-40%[1]
Metabolism Hepatic to inactive metabolites[1]
Half-life 12-16 hours[1]
Excretion urine (72%)[1]
CAS number 4205-90-7 YesY
ATC code C02AC01 N02CX02, S01EA04
PubChem CID 2803
IUPHAR ligand 516
DrugBank DB00575
ChemSpider 2701 YesY
KEGG D00281 YesY
Chemical data
Formula C9H9Cl2N3 
Mol. mass 230.093 g/mol
 YesY (what is this?)  (verify)

Clonidine (trade names Catapres, Kapvay, Nexiclon and others) is a sympatholytic medication used to treat high blood pressure, ADHD, anxiety/panic disorder, and certain pain conditions. It is classified as a centrally acting α2 adrenergic agonist. An alternative hypothesis that has been proposed is that clonidine acts centrally as an imidazoline receptor agonist.

Medical uses[edit]

Clonidine tablets and transdermal patch

Clonidine along with methylphenidate has been studied for treatment of ADHD.[2][3][4] In 2010, the Food and Drug Administration approved the use of clonidine either as an adjunct to traditional stimulant therapy or as a monotherapy in the treatment of ADHD.[1] In Australia, while ADHD is an accepted use for clonidine (which in Australia is only available in immediate release formulations) it has not been approved by the TGA for this indication.[5]

Clonidine can be used in the treatment of Tourette syndrome (specifically for tics).[6]

Clonidine may be used to ease withdrawal symptoms associated with the long-term use of narcotics, alcohol and nicotine (smoking). It can alleviate opioid withdrawal symptoms by reducing the sympathetic nervous system response such as tachycardia and hypertension, as well as reducing sweating, hot and cold flashes, and general restlessness.[7] The sedation effect is also useful although its side effects can include insomnia, thus exacerbating an already common feature of opioid withdrawal.[8]

Clonidine also has several off-label uses, and has been prescribed to treat psychiatric disorders including stress, sleep disorders, and hyperarousal caused by post-traumatic stress disorder, borderline personality disorder, and other anxiety disorders.[9][10][11][12][13][14][15][16][17] Clonidine is also a mild sedative, and can be used as premedication before surgery or procedures.[18] Its epidural use for pain during heart attack, postoperative and intractable pain has also been studied extensively.[19] Clonidine has also been suggested as a treatment for rare instances of dexmedetomidine withdrawal.[20] Clonidine can be used in restless legs syndrome. It can also be used to treat facial flushing and redness associated with rosacea.[21] It has also been successfully used topically in a clinical trial as a treatment for diabetic neuropathy.[22] Clonidine can also be used for migraine headaches and hot flashes associated with menopause.[23][24]

Clonidine suppression test[edit]

Clonidine's effect on reducing circulating epinephrine by a central mechanism was used in the past as an investigatory test for pheochromocytoma,[25] which is a catecholamine-synthesizing tumor, usually of the adrenal medulla. In a clonidine suppression test plasma catecholamines levels are measured before and 3 hours after a 0.3 mg oral test dose has been given to a patient. A positive test occurs if there is no decrease in plasma levels.


Clonidine is classed by the FDA as pregnancy category C. It is not known whether clonidine is harmful to an unborn baby. Additionally, clonidine can pass into breast milk and may harm a nursing baby. Therefore, caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.[26]

Adverse effects[edit]

The principle adverse effects of clonidine are dry mouth, dizziness, hypotension (low blood pressure) and drowsiness.[1]

Adverse effects by incidence[27][28][29]

Very common (>10% incidence) adverse effects include:

  • Dizziness
  • Orthostatic hypotension (a drop in blood pressure that occurs upon standing up. More common when given epidurally)
  • Somnolence (drowsiness; dose-dependent)
  • Dry mouth
  • Headache (dose-dependent)
  • Fatigue
  • Skin reactions (if given transdermally)
  • Hypotension

Common (1-10% incidence) adverse effects include:

  • Anxiety
  • Constipation
  • Sedation (dose-dependent)
  • Nausea/vomiting
  • Malaise
  • Abnormal LFTs
  • Rash
  • Weight gain/loss
  • Pain below the ear (from salivary gland)
  • Erectile Dysfunction

Uncommon (0.1-1% incidence) adverse effects include:

Rare (0.01-0.1% incidence) adverse effects include:

  • Gynaecomastia (swelling of breast tissue in males)
  • Impaired ability to cry
  • Atrioventricular block
  • Nasal dryness
  • Colonic pseudo-obstruction
  • Alopecia (hair loss)
  • Hyperglycemia


Clonidine suppresses sympathetic outflow resulting in lower blood pressure, but sudden discontinuation can cause rebound hypertension due to a rebound in sympathetic outflow.

Clonidine therapy should generally be gradually tapered off when discontinuing therapy to avoid rebound effects from occurring. Treatment of clonidine withdrawal hypertension depends on the severity of the condition. Reintroduction of clonidine for mild cases, alpha and beta blockers for more urgent situations. Beta blockers never should be used alone to treat clonidine withdrawal as alpha vasoconstriction would still continue.[30][31]

Since ADHD drugs like amphetamine and methylphenidate tend to stimulate the sympathetic nervous system, missed doses of clonidine while under ADHD stimulant therapy might entail increased risks of a more severe rebound hypertension. This has not been evaluated.

Interactions with other medications[edit]

  • NSAIDs
  • Medications for depression (ie imipramine, mirtazapine)
  • Medications for mental illness (antipsychotics)
  • Beta Blockers
  • Diuretics
  • Alpha blockers
  • Vasodilators
  • Calcium Antagonists
  • ACE-inhibitors
  • Digitalis

Mechanism of action[edit]

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). The net effect is a decrease in sympathetic tone.[32]

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.[33]

Its 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.[34]

Receptor Ki (nM)[35]
α1A 316.2278
α1B 316.2278
α1D 125.8925
α2A 42.92
α2B 106.31
α2C 233.1


Clonidine, 2-(2,6-dichlorophenylamino)imidazoline, is synthesized from 2,6-dichloroaniline, the reaction of which with ammonium thiocyanate gives N-(2,6- dichlorophenyl)thiourea. Methylation of this product, followed by the subsequent reaction with ethylene diamine gives clonidine. Clonidine synthesis.png

Clonidine Synthesis.png

US patent 3937717, Stahle, H.; Koppe, H.; Kummer, W.; Stockhaus, K., "2-Phenylamino-imidazolines-(2)", issued 1976-02-10, assigned to Boehringer Ingelheim GmbH 

[36] == When to take Special Care == The following are conditions that patients should take special care before taking Clonidine:

  • Raynaud's disease
  • Heart or kidney problems
  • Depression
  • Constipation
  • Paresthesia
  • Dry eyes with contacts

Clonidine and Alcohol Use[edit]

Alcohol use with clonidine can lead to increased drowsiness, dizziness, or visual disturbances with clonidine use. If true, do not operate machinery or drive.


  1. ^ a b c d e f g "clonidine (Rx) - Catapres, Catapres-TTS, more..". Medscape Reference. WebMD. Retrieved 10 November 2013. 
  2. ^ Kornfield R, Watson S, Higashi A, Dusetzina S, Conti R, Garfield R, Dorsey ER, Huskamp HA, Alexander GC; Watson; Higashi; Conti; Dusetzina; Garfield; Dorsey; Huskamp; Alexander (April 2013). "Impact of FDA Advisories on Pharmacologic Treatment of Attention Deficit Hyperactivity Disorder". Psychiatric Services 64 (4): 339–46. doi:10.1176/ PMID 23318985. 
  3. ^ Daviss, W.; Patel, N.; Robb, A.; McDermott, M.; Bukstein, O.; Pelham Jr, W.; Palumbo, D.; Harris, P.; Sallee, F. (2008). "Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis". Journal of the American Academy of Child and Adolescent Psychiatry 47 (2): 189–198. doi:10.1097/chi.0b013e31815d9ae4. PMID 18182964.  edit
  4. ^ Palumbo, D.; Sallee, F.; Pelham, W., Jr; Bukstein, O.; Daviss, W.; McDermott, M. (2008). "Clonidine for attention-deficit / hyperactivity disorder: I. Efficacy and tolerability outcomes". Journal of the American Academy of Child and Adolescent Psychiatry 47 (2): 180–188. doi:10.1097/chi.0b013e31815d9af7. PMID 18182963.  edit
  5. ^ Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.  edit
  6. ^ Schapiro, N. A. (2002). "Dude, you don't have Tourette's". Pediatr. Nurs. 3 (28): 243–246, 249–253. PMID 12087644. 
  7. ^ Giannini, A. J. (1997). Drugs of Abuse (2nd ed.). Los Angeles: Practice Management Information. 
  8. ^ Giannini, A. J.; Extein, I.; Gold, M. S.; Pottash, A. L. C.; Castellani, S. (1983). "Clonidine in mania". Drug Development Research 3 (1): 101–105. doi:10.1002/ddr.430030112. 
  9. ^ Ziegenhorn, A.; Roepke, S.; Schommer, N.; Merkl, A.; Danker-Hopfe, H.; Perschel, F.; Heuser, I.; Anghelescu, I.; Lammers, C. (2009). "Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial". Journal of Clinical Psychopharmacology 29 (2): 170–173. doi:10.1097/JCP.0b013e31819a4bae. PMID 19512980.  edit
  10. ^ Najjar, F.; Weller, R. A.; Weisbrot, J.; Weller, E. B. (2008). "Post-traumatic stress disorder and its treatment in children and adolescents". Current Psychiatry Reports 10 (2): 104–108. doi:10.1007/s11920-008-0019-0. PMID 18474199.  edit
  11. ^ Huffman, J. C.; Stern, T. A. (2007). "Neuropsychiatric consequences of cardiovascular medications". Dialogues in Clinical Neuroscience 9 (1): 29–45. PMC 3181843. PMID 17506224.  edit
  12. ^ Boehnlein, J.; Kinzie, J. (2007). "Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin". Journal of Psychiatric Practice 13 (2): 72–78. doi:10.1097/01.pra.0000265763.79753.c1. PMID 17414682.  edit
  13. ^ Strawn, J.; Geracioti, T., Jr (2008). "Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder". Depression and Anxiety 25 (3): 260–271. doi:10.1002/da.20292. PMID 17354267.  edit
  14. ^ Southwick, S. M.; Bremner, J. D.; Rasmusson, A.; Morgan, C. A. 3rd; Arnsten, A.; Charney, D. S. (1999). "Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder". Biological Psychiatry 46 (9): 1192–1204. doi:10.1016/S0006-3223(99)00219-X. PMID 10560025.  edit
  15. ^ Sutherland, S. M.; Davidson, J. R. (1994). "Pharmacotherapy for post-traumatic stress disorder". The Psychiatric Clinics of North America 17 (2): 409–423. PMID 7937367.  edit
  16. ^ Van Der Kolk, B. A. (1987). "The drug treatment of post-traumatic stress disorder". Journal of Affective Disorders 13 (2): 203–213. doi:10.1016/0165-0327(87)90024-3. PMID 2960712.  edit
  17. ^ "Understanding Comorbid Depression and Anxiety". 
  18. ^ Fazi, L.; Jantzen, E. C.; Rose, J. B.; Kurth, C. D.; Watcha, M. F. (2001). "A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient" (pdf). Anesthesia and Analgesia 92 (1): 56–61. PMID 11133600. 
  19. ^ Patel, S. S.; Dunn, C. J.; Bryson, H. M. (1996). "Epidural clonidine: a review of its pharmacology and efficacy in the management of pain during labour and postoperative and intractable pain". CNS Drugs 6 (6): 474–497. doi:10.2165/00023210-199606060-00007. 
  20. ^ Kukoyi, A. T.; Coker, S. A.; Lewis, L. D.; Nierenberg, D. W. (January 2013). "Two cases of acute dexmedetomidine withdrawal syndrome following prolonged infusion in the intensive care unit: Report of cases and review of the literature". Human and Experimental Toxicology 32 (1): 107–110. doi:10.1177/0960327112454896. PMID 23111887. Retrieved 1 March 2013. 
  21. ^ Blount, B. W.; Pelletier, A. L. (2002). "Rosacea: A Common, Yet Commonly Overlooked, Condition". American Family Physician 66 (3): 435–441. PMID 12182520. 
  22. ^ Campbell, CM; Kipnes, MS; Stouch, BC; Brady, KL; Kelly, M; Schmidt, WK; Petersen, KL; Rowbotham, MC; Campbell, JN (September 2012). "Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy" (PDF). Pain 153 (9): 1815–1823. doi:10.1016/j.pain.2012.04.014. PMC 3413770. PMID 22683276. 
  23. ^ "Clonidine Oral Uses". Web MD. 
  24. ^ "Clonidine". 
  25. ^ Eisenhofer, G.; Goldstein, D. S.; Walther, M. M. et al. (2003). "Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results". J. Clin. Endocrinol. Metab. 88 (6): 2656–2666. doi:10.1210/jc.2002-030005. PMID 12788870. 
  26. ^ "Clonidine". Prescription Marketed Drugs. 
  27. ^ "CATAPRES® 150 TABLETS CATAPRES® AMPOULES" (PDF). TGA eBusiness Services. Boehringer Ingelheim Pty Limited. 28 February 2013. Retrieved 27 November 2013. 
  28. ^ "CATAPRES (clonidine hydrochloride) tablet [Boehringer Ingelheim Pharmaceuticals Inc.]". DailyMed. Boehringer Ingelheim Pharmaceuticals Inc. June 2012. Retrieved 27 November 2013. 
  29. ^ "Clonidine 25 mcg Tablets BP - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sandoz Limited. 2 August 2012. Retrieved 27 November 2013. 
  30. ^ Parker, K.; Brunton, L.; Goodman, L. S.; Lazo, J. S.; Gilman, A. (2006). Goodman & Gilman's - the pharmacological basis of therapeutics. New York: McGraw-Hill. pp. 854–855. ISBN 0-07-142280-3. 
  31. ^ Vitiello, B. (2008). "Understanding the Risk of Using Medications for ADHD with Respect to Physical Growth and Cardiovascular Function". Child Adolesc Psychiatr Clin N Am 17 (2): 459–474, xi. doi:10.1016/j.chc.2007.11.010. PMC 2408826. PMID 18295156. 
  32. ^ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 12. ISBN 1-59541-101-1. 
  33. ^ Reis, D. J.; Piletz, J. E. (1997). "The imidazoline receptor in control of blood pressure by clonidine and drugs" (pdf). American Journal of Physiology 273 (5): R1569–R1571. PMID 9374795. 
  34. ^ "The Role of Alpha 2 Agonists in the Attention Deficit/Hyperactivity Disorder Treatment Paradigm". Medscape Reference. WebMD. 2008. Retrieved 15 November 2013. 
  35. ^ Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 25 November 2013. 
  36. ^ "Catapres Tablets 100 mg". Boehringer Ingelheim. Retrieved 2014-04-19. 

External links[edit]