View source for Clonidine

{{Short description|Alpha-2 adrenergic receptor agonist}}
{{Distinguish|Chlornidine}}
{{Use dmy dates|date=February 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| image = Clonidine2DACS3.svg
| image_class = skin-invert-image
| width = 150
| alt = 
| image2 = Clonidine ball-and-stick model.png
| image_class2 = bg-transparent
| width2 = 150
| alt2 = 
| caption = 

<!-- Clinical data -->
| pronounce = {{IPAc-en|ˈ|k|l|ɒ|n|ə|d|iː|n}}
| tradename = Catapres, others
| Drugs.com = {{drugs.com|monograph|clonidine}}
| MedlinePlus = a682243
| DailyMedID = Clonidine
| pregnancy_AU = B3
| routes_of_administration = [[By mouth]], [[Epidural administration|epidural]], [[Intravenous therapy|intravenous]], [[transdermal]], [[Topical medication|topical]]
| class = [[Alpha-2 adrenergic receptor|α<sub>2A</sub>-adrenergic receptor agonist]] and [[Sedative]]
| ATC_prefix = C02
| ATC_suffix = AC01
| ATC_supplemental = 

<!-- Legal status -->
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
| legal_US_comment = <ref>{{cite web | title=Catapres-TTS-1- clonidine transdermal system patch; Catapres-TTS-2- clonidine transdermal system patch; Catapres-TTS-3- clonidine transdermal system patch | website=DailyMed | date=25 March 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d4a55825-7041-42f4-b3b2-dd7a25dbe793 | access-date=5 September 2024}}</ref><ref>{{cite web | title=Onyda XR- clonidine hydrochloride suspension, extended release | website=DailyMed | date=7 June 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4a15c850-9da5-4bdc-a34d-7f740a6149b7 | access-date=5 September 2024}}</ref>

<!-- Pharmacokinetic data -->
| bioavailability = 70–80% (oral),<ref name="davies"/><ref name="DailyMed II">{{cite web | title=Catapres- clonidine hydrochloride tablet | website=DailyMed | date=6 September 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | access-date=21 December 2019 | quote=The pharmacokinetics of clonidine is dose-proportional in the range of 100 to 600 µg.The absolute bioavailability of clonidine on oral administration is 70% to 80%. Peak plasma clonidine levels are attained in approximately 1 to 3 hours. | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | url-status=live }}</ref> 60–70% (transdermal)<ref name = clinp>{{cite journal | vauthors = Lowenthal DT, Matzek KM, MacGregor TR | title = Clinical pharmacokinetics of clonidine | journal = Clinical Pharmacokinetics | volume = 14 | issue = 5 | pages = 287–310 | date = May 1988 | pmid = 3293868 | doi = 10.2165/00003088-198814050-00002 | s2cid = 24783447 }}</ref>
| protein_bound = 20–40%<ref name = MSR/>
| metabolism = [[Liver]] to inactive [[metabolite]]s,<ref name = MSR/> 2/3 [[CYP2D6]]<ref name="cypmetabolism">{{cite journal | vauthors = Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF | title = CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance | journal = Drug Metabolism and Disposition | volume = 38 | issue = 9 | pages = 1393–1396 | date = September 2010 | pmid = 20570945 | doi = 10.1124/dmd.110.033878 | pmc = 2939473 }}</ref>
| elimination_half-life = IR: 12–16 hours; 41 hours in [[kidney failure]],<ref name="DailyMed III">{{cite web | title=Catapres- clonidine hydrochloride tablet | website=DailyMed | date=6 September 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | access-date=21 December 2019 | quote=Following intravenous administration, clonidine displays biphasic disposition with a distribution half-life of about 20 minutes and an elimination half-life ranging from 12 to 16 hours. The half-life increases up to 41 hours in patients with severe impairment of renal function. Clonidine crosses the placental barrier. It has been shown to cross the blood–brain barrier in rats. | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | url-status=live }}</ref><ref>{{cite web |url=http://www.rxlist.com/kapvay-drug/clinical-pharmacology.htm |title=Kapvay |website=RxList |access-date=30 October 2014 |archive-date=12 October 2017 |archive-url=https://web.archive.org/web/20171012000817/https://www.ncbi.nlm.nih.gov/pubmed/20570945 |url-status=live }}</ref> 48 hours for repeated dosing<ref name = clinp/>
| duration_of_action = Blood pressure:
{{plainlist|
*≤ 8 hours}}
| excretion = [[Urine]] (72%)<ref name="MSR">{{cite web|title=clonidine (Rx) - Catapres, Catapres-TTS, more..|work=Medscape Reference|publisher=WebMD|access-date=10 November 2013|url=http://reference.medscape.com/drug/catapres-tts-clonidine-342382|archive-date=4 December 2020|archive-url=https://web.archive.org/web/20201204171104/https://reference.medscape.com/drug/catapres-tts-clonidine-342382|url-status=live}}</ref>
| onset = IR: 30–60 minutes after an oral dose<ref name="DailyMed 2016">{{cite web | title=Catapres- clonidine hydrochloride tablet | website=DailyMed | date=6 September 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | access-date=21 December 2019 | quote=Catapres tablets act relatively rapidly. The patient's blood pressure declines within 30 to 60 minutes after an oral dose, the maximum decrease occurring within 2 to 4 hours. | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | url-status=live }}</ref>

<!-- Identifiers -->
| CAS_number = 4205-90-7
| PubChem = 2803
| IUPHAR_ligand = 516
| DrugBank = DB00575
| ChemSpiderID = 2701
| UNII = MN3L5RMN02
| KEGG = D00281
| ChEBI = 3757
| ChEMBL = 134
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = 

<!-- Chemical and physical data -->
| IUPAC_name = ''N''-(2,6-Dichlorophenyl)-4,5--1''H''-imidazol-2-amine
| C = 9
| H = 9
| Cl = 2
| N = 3
| SMILES = Clc1cccc(Cl)c1N/C2=N/CCN2
| StdInChI = 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)
| StdInChIKey = GJSURZIOUXUGAL-UHFFFAOYSA-N
}}

<!-- Definition and medical uses -->
'''Clonidine''', sold under the brand name '''Catapres''' among others, is an [[Alpha-2 adrenergic receptor|α<sub>2A</sub>-adrenergic receptor agonist]],  [[hypotensive]] and [[anxiolytic]] agent<ref name="Goodman13">{{cite book| vauthors = Westfall TC, Macarthur H, Westfall DP |title=Goodman and Gilman's The Pharmacological Basis of Therapeutics|date=2017|publisher=McGraw-Hill Education / Medical|isbn=978-1-259-58473-2 | veditors = Brunton L, Knollmann B, Hilal-Dandan R |edition=13th|chapter=Chapter 12:Adrenergic Agonists and Antagonists}}</ref> used to treat [[hypertension|high blood pressure]], [[attention deficit hyperactivity disorder]] (ADHD), [[drug withdrawal]] (e.g., [[Alcohol withdrawal syndrome|alcohol]], [[Opioid withdrawal|opioids]], or [[Nicotine withdrawal|nicotine]]), [[menopause|menopausal flushing]], [[diarrhea]], [[spasticity]], and certain pain conditions.<ref name="AHFS2019">{{cite web |title=Clonidine Monograph for Professionals |url=https://www.drugs.com/monograph/clonidine.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=2 February 2019 |archive-date=3 February 2019 |archive-url=https://web.archive.org/web/20190203030724/https://www.drugs.com/monograph/clonidine.html |url-status=live }}</ref> The drug is often prescribed off-label for [[Tic|tics]]. It is used [[oral administration|orally]] (by mouth), by [[Injection (medicine)|injection]], or as a [[transdermal]] skin patch.<ref name="AHFS2019" /> Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.<ref name="AHFS2019" /> [[Xylazine]] is a [[structural analog]] of [[clonidine]].

<!-- Side effects and mechanism -->
Common side effects include [[dry mouth]], [[dizziness]], [[Headache|headaches]], [[hypotension]], and [[sleepiness]].<ref name="AHFS2019" /> Severe side effects may include [[hallucinations]], [[heart arrhythmias]], and [[confusion]].<ref name="BNF76">{{cite book|title=British national formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=978-0-85711-338-2|pages=144|edition=76}}</ref> If rapidly stopped, withdrawal effects may occur, such as [[hypertensive emergency|a dangerous rise in blood pressure]].<ref name="AHFS2019" /> Use during [[pregnancy]] or [[breastfeeding]] is not recommended.<ref name="BNF76" /> Clonidine lowers blood pressure by stimulating [[Alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptors]] in the brain, which results in relaxation of many arteries.<ref name="AHFS2019" />

<!-- History and culture -->
Clonidine was patented in 1961 and came into medical use in 1966.<ref>{{cite journal | vauthors = Neil MJ | title = Clonidine: clinical pharmacology and therapeutic use in pain management | journal = Current Clinical Pharmacology | volume = 6 | issue = 4 | pages = 280–287 | date = November 2011 | pmid = 21827389 | doi = 10.2174/157488411798375886 | s2cid = 40756251 }}</ref><ref>{{cite journal| vauthors = Stähle H |title=A historical perspective: development of clonidine|journal=Best Practice & Research Clinical Anaesthesiology|date=June 2000|volume=14|issue=2|pages=237–246|doi=10.1053/bean.2000.0079}}</ref><ref name=Fis2006>{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=550 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA550 |access-date=12 September 2020 |archive-date=29 April 2023 |archive-url=https://web.archive.org/web/20230429051619/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA550 |url-status=live }}</ref> It is available as a [[generic medication]].<ref name=AHFS2019/> In 2023, it was the 82nd most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions.<ref name="Top300Drugs">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Clonidine Drug Usage Statistics, United States, 2013 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Clonidine | access-date = 18 August 2025 }}</ref>
{{TOC limit}}

==Medical uses==
[[Image:Clonidine pills and patch.jpg|thumb|left|200px|Clonidine tablets and transdermal patch]]

Clonidine is used to treat [[hypertension|high blood pressure]], [[attention deficit hyperactivity disorder]] (ADHD); [[drug withdrawal]], including from ([[Alcohol withdrawal syndrome|alcohol]], [[Opioid withdrawal|opioids]], and/or [[Nicotine withdrawal|nicotine]]); [[menopause|menopausal flushing]], [[diarrhea]], and certain pain conditions. In addition, it also sees some use off-label for episodic [[insomnia]], and [[tics]] (e.g. from [[Tourette Syndrome|Tourette syndrome]], [[restless legs syndrome]], and [[anxiety]], among others).<ref name=AHFS2019/>

===Resistant hypertension===
Clonidine may be effective for lowering blood pressure in people with [[Hypertension#Resistant hypertension|resistant hypertension]].<ref>{{cite journal |vauthors=Viera AJ |title=Hypertension Update: Resistant Hypertension |journal=FP Essent |volume=469 |pages=20–25 |date=June 2018 |pmid=29863319 }}</ref>

Clonidine works by slowing the [[pulse rate]] and exerts a reduction of serum concentrations of [[renin]], [[aldosterone]], and [[catecholamines]].<ref name="DailyMed">{{cite web | title=Catapres- clonidine hydrochloride tablet | website=DailyMed | date=6 September 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | access-date=21 December 2019 | quote=Slowing of the pulse rate has been observed in most patients given clonidine, but the drug does not alter normal hemodynamic response to exercise. Other studies in patients have provided evidence of a reduction in plasma renin activity and in the excretion of aldosterone and catecholamines. | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | url-status=live }}</ref>

===Attention deficit hyperactivity disorder===
Clonidine may improve symptoms of attention deficit hyperactivity disorder in some people but causes many adverse effects and the beneficial effect is modest.<ref>{{cite journal | vauthors = Connor DF, Fletcher KE, Swanson JM | title = A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 38 | issue = 12 | pages = 1551–1559 | date = December 1999 | pmid = 10596256 | doi = 10.1097/00004583-199912000-00017 }}</ref> In [[Australia]], clonidine is an accepted but not approved use for ADHD by the [[Therapeutic Goods Administration]].<ref name="AMH">{{cite book | editor = Rossi, S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref> Clonidine, along with [[methylphenidate]], has been studied for treatment of ADHD.<ref name="Clonidine for attention-deficit">{{cite journal | vauthors = Palumbo DR, Sallee FR, Pelham WE, Bukstein OG, Daviss WB, McDERMOTT MP | title = Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 47 | issue = 2 | pages = 180–188 | date = February 2008 | pmid = 18182963 | doi = 10.1097/chi.0b013e31815d9af7 }}</ref><ref>{{cite journal | vauthors = Daviss WB, Patel NC, Robb AS, McDERMOTT MP, Bukstein OG, Pelham WE, Palumbo D, Harris P, Sallee FR | title = Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 47 | issue = 2 | pages = 189–198 | date = February 2008 | pmid = 18182964 | doi = 10.1097/chi.0b013e31815d9ae4 }}</ref><ref name="Effects">{{cite journal | vauthors = Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, Dorsey ER, Huskamp HA, Alexander GC | title = Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008 | journal = Psychiatric Services | volume = 64 | issue = 4 | pages = 339–346 | date = April 2013 | pmid = 23318985 | pmc = 4023684 | doi = 10.1176/appi.ps.201200147 }}</ref> While not as effective as methylphenidate in treating ADHD, clonidine does offer some benefit;<ref name="Clonidine for attention-deficit" /> it can also be useful in combination with [[stimulant]] medications.<ref>{{cite journal | vauthors = Kollins SH, Jain R, Brams M, Segal S, Findling RL, Wigal SB, Khayrallah M | title = Clonidine extended-release tablets as add-on therapy to psychostimulants in children and adolescents with ADHD | journal = Pediatrics | volume = 127 | issue = 6 | pages = e1406–e1413 | date = June 2011 | pmid = 21555501 | pmc = 3387872 | doi = 10.1542/peds.2010-1260 }}</ref> Some studies show clonidine to be more [[Sedation|sedating]] than [[guanfacine]], which may be better at bedtime along with an arousing [[stimulant]] in the morning.<ref>{{cite journal | vauthors = Jäkälä P, Riekkinen M, Sirviö J, Koivisto E, Kejonen K, Vanhanen M, Riekkinen P | title = Guanfacine, but not clonidine, improves planning and working memory performance in humans | journal = Neuropsychopharmacology | volume = 20 | issue = 5 | pages = 460–470 | date = May 1999 | pmid = 10192826 | doi = 10.1016/S0893-133X(98)00127-4 | doi-access = free }}</ref><ref>{{Cite journal |url = http://cpnp.org/resource/mhc/2014/01/clonidine-and-guanfacine-ir-vs-er-old-drugs-new-formulations |title = Clonidine and Guanfacine IR vs ER: Old Drugs With "New" Formulations |access-date = 1 August 2014 |journal = Mental Health Clinician |year = 2014 |doi = 10.9740/mhc.n186955 |vauthors = Freeland K, Turner A, Gormley L |volume = 4 |pages = 22–26 |doi-access = free |archive-date = 9 August 2014 |archive-url = https://web.archive.org/web/20140809181310/http://cpnp.org/resource/mhc/2014/01/clonidine-and-guanfacine-ir-vs-er-old-drugs-new-formulations |url-status = live }}</ref> Clonidine has been used to reduce sleep disturbances in ADHD, including to help offset stimulant-associated [[insomnia]].<ref name="pmid24027233">{{cite journal | vauthors = Nguyen M, Tharani S, Rahmani M, Shapiro M | title = A review of the use of clonidine as a sleep aid in the child and adolescent population | journal = Clinical Pediatrics | volume = 53 | issue = 3 | pages = 211–216 | date = March 2014 | pmid = 24027233 | doi = 10.1177/0009922813502123 | s2cid = 742140 }}</ref><ref name="pmid15853572">{{cite journal | vauthors = Hoban TF | title = Assessment and treatment of disturbed sleep in attention deficit hyperactivity disorder | journal = Expert Review of Neurotherapeutics | volume = 4 | issue = 2 | pages = 307–316 | date = March 2004 | pmid = 15853572 | doi = 10.1586/14737175.4.2.307 | s2cid = 35000868 }}</ref><ref name="SchacharIckowicz1999">{{cite book | editor-first = | title = Handbook of Disruptive Behavior Disorders | vauthors = Schachar R, Ickowicz A | chapter = Pharmacological Treatment of Attention-Deficit/HyperactivityDisorder | date = 1999 | pages = 221–254 | publisher = Springer US | doi = 10.1007/978-1-4615-4881-2_10 | isbn = 978-1-4613-7214-1| url = }}</ref><ref name="pmid8169189">{{cite journal | vauthors = Wilens TE, Biederman J, Spencer T | title = Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 33 | issue = 3 | pages = 424–426 | date = 1994 | pmid = 8169189 | doi = 10.1097/00004583-199403000-00018 }}</ref> Unlike stimulant medications, clonidine is regarded as having no abuse potential, and may even be used to reduce abuse of drugs including nicotine and cocaine.<ref name="Walker2014">{{cite journal | vauthors = Clemow DB, Walker DJ | title = The potential for misuse and abuse of medications in ADHD: a review | journal = Postgraduate Medicine | volume = 126 | issue = 5 | pages = 64–81 | date = September 2014 | pmid = 25295651 | doi = 10.3810/pgm.2014.09.2801 | s2cid = 207580823 }}</ref>

In the US, only the extended-release form of clonidine is approved for ADHD treatment.<ref name="FDA_PI">{{cite web |title=Highlights of Prescribing Information: Kapvay |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022331s014lbl.pdf |archive-url=https://web.archive.org/web/20160327193722/http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022331s014lbl.pdf |archive-date=27 March 2016 |publisher=US FDA |access-date=31 March 2024}}</ref>

=== Borderline personality disorder ===
Clonidine has been studied off-label in borderline personality disorder (BPD) to address specific acute symptoms such as hyperarousal, inner tension, dissociation, self-injurious urges, and sleep disturbances.{{Citation needed|date=July 2025}}

A systematic review of psychopharmacology in BPD identified clonidine as a promising adjunctive therapy targeting noradrenergic dysregulation, especially in comorbid PTSD cases. However, it emphasized the limitations of small sample sizes and called for larger placebo-controlled trials.<ref>Stoffers, J. M., & Lieb, K. (2015). Pharmacotherapy for borderline personality disorder—symptom targeted and disorder specific treatment options. ''Current Pharmaceutical Design, 21''(23), 3301–3311.</ref>

Clinicians often employ clonidine when BPD patients present with acute emotional dysregulation, intrusive dissociation, or insomnia. Clinical anecdotal reports and patient experiences have also highlighted its practical utility.{{Citation needed|date=July 2025}}

===Drug withdrawal===
Clonidine may be used to ease drug withdrawal symptoms associated with abruptly stopping the long-term use of [[opioids]], [[alcohol (drug)|alcohol]], [[benzodiazepines]], and [[nicotine]].<ref>{{cite journal | vauthors = Fitzgerald PJ | title = Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine | journal = Substance Abuse | volume = 7 | pages = 171–183 | date = October 2013 | pmid = 24151426 | pmc = 3798293 | doi = 10.4137/SART.S13019 }}</ref> It can alleviate [[opioid withdrawal]] symptoms by reducing the [[sympathetic nervous system]] response such as [[tachycardia]] and [[hypertension]], [[hyperhidrosis]] (excessive sweating), hot and cold flashes, and [[akathisia]].<ref>{{ cite book | vauthors = Giannini AJ | title = Drugs of Abuse | edition = 2nd | location = Los Angeles | publisher = Practice Management Information | year = 1997 }}</ref> It may also be helpful in aiding smokers to quit.<ref>{{cite journal | vauthors = Gourlay SG, Stead LF, Benowitz NL | title = Clonidine for smoking cessation | journal = The Cochrane Database of Systematic Reviews | volume = 2008 | issue = 3 | article-number = CD000058 | date = 2004 | pmid = 15266422 | pmc = 7038651 | doi = 10.1002/14651858.CD000058.pub2 }}</ref> The sedation effect can also be useful. Clonidine may also reduce severity of [[neonatal withdrawal|neonatal abstinence syndrome]] in infants born to mothers that are using certain drugs, particularly opioids.<ref>{{cite journal | vauthors = Streetz VN, Gildon BL, Thompson DF | title = Role of Clonidine in Neonatal Abstinence Syndrome: A Systematic Review | journal = The Annals of Pharmacotherapy | volume = 50 | issue = 4 | pages = 301–310 | date = April 2016 | pmid = 26783353 | doi = 10.1177/1060028015626438 | s2cid = 40652097 }}</ref> In infants with neonatal withdrawal syndrome, clonidine may improve the [[neonatal intensive care unit]] Network Neurobehavioral Score.<ref>{{cite journal | vauthors = Disher T, Gullickson C, Singh B, Cameron C, Boulos L, Beaubien L, Campbell-Yeo M | title = Pharmacological Treatments for Neonatal Abstinence Syndrome: A Systematic Review and Network Meta-analysis | journal = JAMA Pediatrics | volume = 173 | issue = 3 | pages = 234–243 | date = March 2019 | pmid = 30667476 | pmc = 6439896 | doi = 10.1001/jamapediatrics.2018.5044 }}</ref>

Clonidine has also been suggested as a treatment for rare instances of [[dexmedetomidine]] withdrawal.<ref>{{cite journal | vauthors=Kukoyi A, Coker S, Lewis L, Nierenberg D | title = Two cases of acute dexmedetomidine withdrawal syndrome following prolonged infusion in the intensive care unit: Report of cases and review of the literature | journal = Human & Experimental Toxicology |date=January 2013 | volume = 32 |issue = 1 | pages = 107–110 | doi = 10.1177/0960327112454896 | pmid = 23111887 | s2cid = 31570614 }}</ref>

=== Spasticity ===
Clonidine has some role in the treatment of spasticity caused by spinal cord injury, acting principally by inhibiting excessive sensory transmission{{clarify span|below the level of injury.|date=March 2024}} Its use, however, is mainly as a second or third line agent, due to side effects such as [[hypotension]], [[bradycardia]], and [[drowsiness]].<ref>{{cite journal | vauthors = Chang E, Ghosh N, Yanni D, Lee S, Alexandru D, Mozaffar T | title = A Review of Spasticity Treatments: Pharmacological and Interventional Approaches | journal = Critical Reviews in Physical and Rehabilitation Medicine | volume = 25 | issue = 1–2 | pages = 11–22 | date = 2013 | pmid = 25750484 | pmc = 4349402 | doi = 10.1615/CritRevPhysRehabilMed.2013007945 }}</ref> Clonidine can be administered [[intrathecal]]ly,<ref name="PMID18443642">{{cite journal | vauthors = Smith HS, Deer TR, Staats PS, Singh V, Sehgal N, Cordner H | title = Intrathecal drug delivery | journal = Pain Physician | volume = 11 | issue = 2 Suppl | pages = S89–S104 | date = March 2008 | doi = 10.36076/ppj.2008/11/S89 | pmid = 18443642 }}</ref> which confers various benefits, including a reduction or prevention of the blood pressure lowering effects and increased effectiveness against spasticity.<ref name="PMID11723871">{{cite journal | vauthors = Rémy-Néris O, Denys P, Bussel B | title = Intrathecal clonidine for controlling spastic hypertonia | journal = Physical Medicine and Rehabilitation Clinics of North America | volume = 12 | issue = 4 | pages = 939–51, ix | date = November 2001 | doi = 10.1016/S1047-9651(18)30040-8 | pmid = 11723871 }}</ref> The effectiveness of intrathecal clonidine is comparable to that of intrathecal baclofen for spasticity.<ref name=PMID11723871/>

===Clonidine suppression test===
The reduction in circulating norepinephrine by clonidine was used in the past as an investigatory test for [[phaeochromocytoma]], which is a [[Neuroendocrine tumor|catecholamine-synthesizing tumor]], usually found in the [[adrenal medulla]].<ref name="pmid12788870">{{cite journal | vauthors = Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR, Pacak K | title = Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 6 | pages = 2656–2666 | date = June 2003 | pmid = 12788870 | doi = 10.1210/jc.2002-030005 | doi-access = free }}</ref> In a clonidine suppression test, plasma catecholamine levels are measured before and 3 hours after a 0.3&nbsp;mg oral test dose has been given to the patient. A positive test occurs if there is no decrease in plasma levels.<ref name="pmid12788870"/>

===Other uses===
Clonidine also has several [[off-label use]]s, and has been prescribed to treat [[psychiatric disorder]]s including [[Stress (biology)|stress]], [[Fight-or-flight response|hyperarousal]] caused by [[post-traumatic stress disorder]], [[borderline personality disorder]], and other [[anxiety disorder]]s.<ref>{{cite journal | vauthors = van der Kolk BA | title = The drug treatment of post-traumatic stress disorder | journal = Journal of Affective Disorders | volume = 13 | issue = 2 | pages = 203–213 | date = September–October 1987 | pmid = 2960712 | doi = 10.1016/0165-0327(87)90024-3 }}</ref><ref>{{cite journal | vauthors = Sutherland SM, Davidson JR | title = Pharmacotherapy for post-traumatic stress disorder | journal = The Psychiatric Clinics of North America | volume = 17 | issue = 2 | pages = 409–423 | date = June 1994 | pmid = 7937367 | doi = 10.1016/S0193-953X(18)30122-9 }}</ref><ref>{{cite journal | vauthors = Southwick SM, Bremner JD, Rasmusson A, Morgan CA, Arnsten A, Charney DS | title = Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder | journal = Biological Psychiatry | volume = 46 | issue = 9 | pages = 1192–1204 | date = November 1999 | pmid = 10560025 | doi = 10.1016/S0006-3223(99)00219-X | s2cid = 32148292 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Strawn JR, Geracioti TD | title = Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder | journal = Depression and Anxiety | volume = 25 | issue = 3 | pages = 260–271 | date = 2008 | pmid = 17354267 | doi = 10.1002/da.20292 | s2cid = 33940152 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Boehnlein JK, Kinzie JD | title = Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin | journal = Journal of Psychiatric Practice | volume = 13 | issue = 2 | pages = 72–78 | date = March 2007 | pmid = 17414682 | doi = 10.1097/01.pra.0000265763.79753.c1 | s2cid = 1607064 }}</ref><ref>{{cite journal | vauthors = Huffman JC, Stern TA | title = Neuropsychiatric consequences of cardiovascular medications | journal = Dialogues in Clinical Neuroscience | volume = 9 | issue = 1 | pages = 29–45 | date = 2007 | pmid = 17506224 | pmc = 3181843 | doi = 10.31887/DCNS.2007.9.1/jchuffman }}</ref><ref>{{cite journal | vauthors = Najjar F, Weller RA, Weisbrot J, Weller EB | title = Post-traumatic stress disorder and its treatment in children and adolescents | journal = Current Psychiatry Reports | volume = 10 | issue = 2 | pages = 104–108 | date = April 2008 | pmid = 18474199 | doi = 10.1007/s11920-008-0019-0 | s2cid = 23494905 }}</ref><ref>{{cite journal | vauthors = Ziegenhorn AA, Roepke S, Schommer NC, Merkl A, Danker-Hopfe H, Perschel FH, Heuser I, Anghelescu IG, Lammers CH | title = Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial | journal = Journal of Clinical Psychopharmacology | volume = 29 | issue = 2 | pages = 170–173 | date = April 2009 | pmid = 19512980 | doi = 10.1097/JCP.0b013e31819a4bae | s2cid = 31292297 }}</ref> Clonidine is also a mild [[sedative]], and can be used as [[premedication]] before surgery or procedures.<ref name=premed>{{cite journal | vauthors = Fazi L, Jantzen EC, Rose JB, Kurth CD, Watcha MF | title = A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient | journal = Anesthesia and Analgesia | volume = 92 | issue = 1 | pages = 56–61 | date = January 2001 | pmid = 11133600 | doi = 10.1097/00000539-200101000-00011 | s2cid = 18885497 | doi-access = free }}</ref> It has also been studied as a way to calm acute [[mania|manic]] episodes.<ref>{{ cite journal | vauthors = Giannini AJ, Extein I, Gold MS, Pottash AL, Castellani S | title = Clonidine in mania | journal = Drug Development Research | volume = 3 | issue = 1 | pages = 101–105 | year = 1983 | doi = 10.1002/ddr.430030112 |s2cid=85093127 }}</ref> Its epidural use for pain during heart attack, and postoperative and intractable pain has also been studied extensively.<ref>{{cite journal | vauthors = Patel SS, Dunn CJ, Bryson HM | title = Epidural clonidine: a review of its pharmacology and efficacy in the management of pain during labour and postoperative and intractable pain | journal = CNS Drugs | year = 1996 | volume = 6 | issue = 6 | pages = 474–497 | doi = 10.2165/00023210-199606060-00007 |s2cid=72544106 }}</ref> Clonidine can be used in [[restless legs syndrome]].<ref name="RLS medscape">{{cite web |title=Treatment and Management of RLS |url=https://www.medscape.org/viewarticle/522010_6 |website=www.medscape.org |publisher=WebMD LLC |access-date=3 October 2018 |archive-date=29 September 2017 |archive-url=https://web.archive.org/web/20170929042337/http://www.medscape.org/viewarticle/522010_6 |url-status=live }}</ref> It can also be used to treat facial flushing and redness associated with [[rosacea]].<ref>{{cite journal | vauthors = Blount BW, Pelletier AL | title = Rosacea: a common, yet commonly overlooked, condition | journal = American Family Physician | volume = 66 | issue = 3 | pages = 435–440 | date = August 2002 | pmid = 12182520 | url = http://www.aafp.org/afp/2002/0801/p435.html | access-date = 12 February 2012 | archive-date = 26 July 2011 | archive-url = https://web.archive.org/web/20110726103851/http://www.aafp.org/afp/2002/0801/p435.html | url-status = live }}</ref> It has also been successfully used topically in a clinical trial as a treatment for [[diabetic neuropathy]].<ref>{{cite journal | vauthors = Campbell CM, Kipnes MS, Stouch BC, Brady KL, Kelly M, Schmidt WK, Petersen KL, Rowbotham MC, Campbell JN | title = Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy | journal = Pain | volume = 153 | issue = 9 | pages = 1815–1823 | date = September 2012 | pmid = 22683276 | pmc = 3413770 | doi = 10.1016/j.pain.2012.04.014 }}</ref> Clonidine can also be used for [[migraine]] headaches and [[hot flash]]es associated with [[menopause]].<ref name="Web MD">{{cite web | title = Clonidine Oral Uses | url = http://www.webmd.com/drugs/drug-11754-Clonidine.aspx?drugid=11754&drugname=Clonidine | publisher = [[WebMD]] | access-date = 30 May 2007 | archive-date = 25 October 2007 | archive-url = https://web.archive.org/web/20071025030547/http://www.webmd.com/drugs/drug-11754-Clonidine.aspx?drugid=11754&drugname=Clonidine | url-status = live }}</ref><ref>{{cite web | title = Clonidine | url = https://www.drugs.com/clonidine.html | publisher = Drugs.com | access-date = 25 May 2017 | archive-date = 14 April 2017 | archive-url = https://web.archive.org/web/20170414001745/https://www.drugs.com/clonidine.html | url-status = live }}</ref> Clonidine has also been used to treat refractory [[diarrhea]] associated with [[irritable bowel syndrome]], [[fecal incontinence]], diabetes, diarrhea associated with opioid withdrawal, [[Short bowel syndrome|intestinal failure]], [[neuroendocrine tumor]]s, and [[cholera]].<ref>{{cite journal | vauthors = Fragkos KC, Zárate-Lopez N, Frangos CC | title = What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans | journal = Therapeutic Advances in Gastroenterology | volume = 9 | issue = 3 | pages = 282–301 | date = May 2016 | pmid = 27134659 | pmc = 4830099 | doi = 10.1177/1756283X15625586 }}</ref> Clonidine can be used in the treatment of [[Tourette syndrome]] (specifically for [[tics]]).<ref>{{cite journal | vauthors = Egolf A, Coffey BJ | title = Current pharmacotherapeutic approaches for the treatment of Tourette syndrome | journal = Drugs of Today | volume = 50 | issue = 2 | pages = 159–179 | date = February 2014 | pmid = 24619591 | doi = 10.1358/dot.2014.50.2.2097801 }}</ref> Clonidine has also had some success in clinical trials for helping to remove or ameliorate the symptoms of [[hallucinogen persisting perception disorder]] (HPPD).<ref>{{cite journal | vauthors = Martinotti G, Santacroce R, Pettorruso M, Montemitro C, Spano MC, Lorusso M, di Giannantonio M, Lerner AG | title = Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives | journal = Brain Sciences | volume = 8 | issue = 3 | page = 47 | date = March 2018 | pmid = 29547576 | pmc = 5870365 | doi = 10.3390/brainsci8030047 | doi-access = free }}</ref>

Injection of [[Alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptor agonists]] into the knee joint space, including clonidine, may reduce the severity of knee pain after [[Arthroscopy|arthroscopic]] knee surgery.<ref>{{cite journal |vauthors=Ryan TJ, Holyoak R, Vlok R, Melhuish T, Hodge A, Binks M, Hurtado G, White L |title=Intra-articular Alpha-2 Agonists as an Adjunct to Local Anesthetic in Knee Arthroscopy: A Systematic Review and Meta-Analysis |journal=J Knee Surg |volume=32 |issue=2 |pages=138–145 |date=February 2019 |pmid=29534270 |doi=10.1055/s-0038-1636909 |s2cid=3861878 }}</ref>

Light-activated derivatives of clonidine (adrenoswitches) have been developed for research purposes and shown to control pupillary reflex with light in blind mice by topical application.<ref>{{cite journal | vauthors = Prischich D, Gomila AM, Milla-Navarro S, Sangüesa G, Diez-Alarcia R, Preda B, Matera C, Batlle M, Ramírez L, Giralt E, Hernando J, Guasch E, Meana JJ, de la Villa P, Gorostiza P | title = Adrenergic Modulation With Photochromic Ligands | journal = Angewandte Chemie | volume = 60 | issue = 7 | pages = 3625–3631 | date = February 2021 | pmid = 33103317 | doi = 10.1002/anie.202010553 | publisher = Wiley | hdl-access = free | hdl = 2434/778579 }}</ref>

===Pregnancy and breastfeeding===
It is classified by the Australian [[Therapeutic Goods Administration]] as pregnancy category B3, which means that it has shown some detrimental effects on fetal development in animal studies, although the relevance of this to human beings is unknown.<ref name = TGA>{{cite web|title=Catapres 150 Tablets Catapres Ampoules|work=TGA eBusiness Services|publisher=Boehringer Ingelheim Pty Limited|date=28 February 2013|access-date=27 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-02400-3|format=PDF|archive-date=16 January 2017|archive-url=https://web.archive.org/web/20170116171140/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-02400-3|url-status=live}}</ref> Clonidine appears in high concentration in breast milk; a nursing infant's serum clonidine concentration is approximately 2/3 of the mother's.<ref>{{cite book |title=Drugs and Lactation Database (LactMed) |date=2006 |publisher=National Library of Medicine (US) |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK501628/ |access-date=5 January 2019 |chapter=Clonidine |pmid=30000689 |archive-date=5 December 2020 |archive-url=https://web.archive.org/web/20201205111454/https://www.ncbi.nlm.nih.gov/books/NBK501628/ |url-status=live }}</ref> Caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.<ref>{{cite web | url = http://drugsdb.eu/drug.php?d=Clonidine&m=Physicians%20Total%20Care,%20Inc.&id=b65742b7-5db5-41cf-bf69-41700cdd2c59.xml | title = Clonidine | work = Prescription Marketed Drugs | publisher = www.drugsdb.eu | access-date = 2 August 2011 | archive-date = 28 March 2012 | archive-url = https://web.archive.org/web/20120328060203/http://drugsdb.eu/drug.php?d=Clonidine&m=Physicians%20Total%20Care,%20Inc.&id=b65742b7-5db5-41cf-bf69-41700cdd2c59.xml }}</ref>

==Adverse effects==
The principal adverse effects of clonidine are sedation, dry mouth, and hypotension (low blood pressure).<ref name = MSR/>

==Pharmacology==
{| class="wikitable floatright" style="font-size:small;"
|+ Clonidine<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP) | author1-link = Bryan Roth | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=Clonidine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | archive-date = 14 November 2022 | archive-url = https://web.archive.org/web/20221114224224/https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=Clonidine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | url-status = live }}</ref>
|-
! Site !! ''K''<sub>i</sub> (nM) !! Species !! Ref
|-
| {{abbrlink|NET|Norepinephrine transporter}} || >1,000 || Human || <ref name="milan2000"/>
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || >10,000 || Rat || <ref>{{cite journal | vauthors = Matsumoto I, Combs MR, Jones DJ | title = Characterization of 5-hydroxytryptamine1B receptors in rat spinal cord via [125I]iodocyanopindolol binding and inhibition of [3H]-5-hydroxytryptamine release | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 260 | issue = 2 | pages = 614–626 | date = February 1992 | doi = 10.1016/S0022-3565(25)11341-4 | pmid = 1738111 }}</ref>
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || >10,000 || Human || <ref name="PDSP"/>
|-
| [[Alpha-1 adrenergic receptor|α<sub>1A</sub>]] ||316.23|| Human || <ref name="milan2000">{{cite journal | vauthors = Millan MJ, Dekeyne A, Newman-Tancredi A, Cussac D, Audinot V, Milligan G, Duqueyroix D, Girardon S, Mullot J, Boutin JA, Nicolas JP, Renouard-Try A, Lacoste JM, Cordi A | title = S18616, a highly potent, spiroimidazoline agonist at alpha(2)-adrenoceptors: I. Receptor profile, antinociceptive and hypothermic actions in comparison with dexmedetomidine and clonidine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 295 | issue = 3 | pages = 1192–1205 | date = December 2000 | doi = 10.1016/S0022-3565(24)39022-6 | pmid = 11082457 }}</ref>
|-
| [[Alpha-1 adrenergic receptor|α<sub>1B</sub>]] || 316.23 || Human || <ref name="milan2000"/>
|-
| [[Alpha-1 adrenergic receptor|α<sub>1D</sub>]] || 125.89 || Human || <ref name="milan2000"/>
|-
| [[Alpha-2A adrenergic receptor|α<sub>2A</sub>]] || 35.48 &ndash; 61.65 || Human || <ref name="milan2000"/><ref name="Jasper1998">{{cite journal | vauthors = Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, Daunt DA, Bonhaus DW, Eglen RM | title = Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding | journal = Biochemical Pharmacology | volume = 55 | issue = 7 | pages = 1035–1043 | date = April 1998 | pmid = 9605427 | doi = 10.1016/s0006-2952(97)00631-x }}</ref>
|-
| [[Alpha-2B adrenergic receptor|α<sub>2B</sub>]] ||69.18 &ndash; 309.0 || Human || <ref name="Jasper1998" /><ref name="milan2000" />
|-
| [[Alpha-2C adrenergic receptor|α<sub>2C</sub>]] ||134.89 &ndash; 501.2|| Human || <ref name="Jasper1998" /><ref name="milan2000" />
|-
| [[Dopamine D1 receptor|D<sub>1</sub>]] || > 10,000 || Rat || <ref name="Neve1990">{{cite journal | vauthors = Neve KA, Henningsen RA, Kinzie JM, De Paulis T, Schmidt DE, Kessler RM, Janowsky A | title = Sodium-dependent isomerization of dopamine D-2 receptors characterized using [125I]epidepride, a high-affinity substituted benzamide ligand | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 252 | issue = 3 | pages = 1108–1116 | date = March 1990 | doi = 10.1016/S0022-3565(25)20168-9 | pmid = 2138666 }}</ref>
|-
| [[Imidazoline receptor|I<sub>1</sub>]] || 31.62|| Bovine || <ref name="milan2000" />
|-
| [[Imidazoline receptor|I<sub>2</sub>]] (cortex) || >1,000 || Rat || <ref name="milan2000" />
|-
| [[Monoamine oxidase A|MAO-A]] || >1,000 || Rat || <ref name="milan2000" />
|-
| [[Monoamine oxidase B|MAO-B]] || >1,000 || Rat || <ref name="milan2000" />
|-
| [[Sigma receptor|σ]] || >10,000 || Guinea Pig || <ref>{{cite journal | vauthors = Weber E, Sonders M, Quarum M, McLean S, Pou S, Keana JF | title = 1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 83 | issue = 22 | pages = 8784–8788 | date = November 1986 | pmid = 2877462 | doi = 10.1073/pnas.83.22.8784 | pmc = 387016 | bibcode = 1986PNAS...83.8784W | doi-access = free }}</ref>
|- class="sortbottom"
| colspan="4" style="width: 1px;" | <small>The [[Dissociation constant|K<sub>i</sub>]] refers to a drug's affinity for a receptor. The smaller the K<sub>i</sub>, the higher the affinity for that receptor.<ref name="Pharmacology 2009">{{cite book | vauthors = Kenakin T| veditors = Hacker M, Messer W, Bachmann K |title=Pharmacology |url=https://archive.org/details/pharmacologyprim00kena_186 |url-access=limited |date=2009 |publisher=Elsevier |isbn=978-0-12-369521-5|page=[https://archive.org/details/pharmacologyprim00kena_186/page/n70 65] |chapter=Ligand-Receptor Binding and Tissue Response}}</ref> Reported imidazoline-2 binding is measured in the cortex &mdash; I<sub>2</sub> receptor bindings measured in stomach membranes are much lower.<ref>{{cite journal | vauthors = Molderings GJ, Donecker K, Burian M, Simon WA, Schröder DW, Göthert M | title = Characterization of I2 imidazoline and sigma binding sites in the rat and human stomach | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 285 | issue = 1 | pages = 170–177 | date = April 1998 | doi = 10.1016/S0022-3565(24)37390-2 | pmid = 9536007 }}</ref> </small>
|}

===Mechanism of action===
Clonidine crosses the [[blood–brain barrier]].<ref name="DailyMed III"/>

====High blood pressure====
Clonidine treats high blood pressure by stimulating [[Alpha-2 adrenergic receptor|α<sub>2</sub> receptors]] in the brainstem, which decreases [[peripheral vascular resistance]], lowering blood pressure. It has specificity towards the [[presynaptic]] α<sub>2</sub> receptors in the [[vasomotor center]] in the [[brainstem]]. This binding has a [[sympatholytic]] effect, suppresses release of [[norepinephrine]], [[Adenosine triphosphate|ATP]], renin, and [[neuropeptide Y]] which if released would increase [[vascular resistance]].<ref name=Goodman13/>{{rp|201–203}}

Clonidine also acts as an agonist at [[imidazoline receptor|imidazoline-1 (I<sub>1</sub>) receptors]] in the brain, and it is hypothesized that this effect may contribute to reducing blood pressure by reducing signaling in the [[sympathetic nervous system]]; this effect acts upstream of the central [[alpha-2 adrenergic receptor|α<sub>2</sub>]] agonist effect of clonidine.<ref name=Goodman13/>{{rp|201–203}}<ref name=imidazoline>{{cite journal | vauthors = Reis DJ, Piletz JE | title = The imidazoline receptor in control of blood pressure by clonidine and drugs | journal = American Journal of Physiology | year = 1997 | volume = 273 | issue = 5 | pages = R1569–R1571 | pmid = 9374795 |doi=10.1152/ajpregu.1997.273.5.R1569 }}</ref>

Clonidine may also cause [[bradycardia]], theoretically by increasing [[vagal tone|signaling through the vagus nerve]]. When given intravenously, clonidine can temporarily increase blood pressure by stimulating α<sub>1</sub> receptors in [[smooth muscle]]s in blood vessels.<ref name=":0">{{cite journal | vauthors = Giovannitti JA, Thoms SM, Crawford JJ | title = Alpha-2 adrenergic receptor agonists: a review of current clinical applications | language = en-US | journal = Anesthesia Progress | volume = 62 | issue = 1 | pages = 31–39 | date = 2015 | pmid = 25849473 | pmc = 4389556 | doi = 10.2344/0003-3006-62.1.31 }}</ref> This hypertensive effect is not usual when clonidine is given orally or by the [[transdermal]] route.<ref name="Goodman13"/>{{rp|201–203}}

Plasma concentration of clonidine exceeding 2.0&nbsp;ng/mL does not provide further blood pressure reduction.<ref name="DailyMed IV">{{cite web | title=Catapres- clonidine hydrochloride tablet | website=DailyMed | date=6 September 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | access-date=21 December 2019 | quote=The antihypertensive effect is reached at plasma concentrations between about 0.2 and 2.0 ng/mL in patients with normal excretory function. A further rise in the plasma levels will not enhance the antihypertensive effect. | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d | url-status=live }}</ref>

==== Attention deficit hyperactivity disorder ====
[[File:Structural comparison of norepinephrine and clonidine.svg|class=skin-invert-image|thumb|325px|right|Structural comparison between the neurotransmitter norepinephrine and the drug clonidine. Both compounds bind to α<sub>2</sub> adrenergic receptors.<ref name="Cinnamon Review" /> Similarities between the two structures are shown highlighted in red.]]

In the setting of [[attention deficit hyperactivity disorder]] (ADHD), clonidine's molecular mechanism of action occurs due to its [[agonist|agonism]] at the [[alpha-2A adrenergic receptor|α<sub>2A</sub> adrenergic receptor]], the subtype of the [[adrenergic receptor]] that is most principally found in the brain. Within the brain, the α<sub>2A</sub> adrenergic receptors are found within the [[prefrontal cortex]] (PFC), among other areas. The α<sub>2A</sub> adrenergic receptors are found on the [[Chemical synapse#Structure|presynaptic cleft]] of a given neuron, and, when activated by an agonist, the effect on downstream neurons is inhibitory. The inhibition is accomplished by preventing the secretion of the neurotransmitter [[norepinephrine]]. Thus, clonidine's agonism on α<sub>2A</sub> adrenergic receptors in the PFC inhibits the action of downstream neurons by preventing the secretion of norepinephrine.<ref name="Cinnamon Review">{{cite journal | vauthors = Cinnamon Bidwell L, Dew RE, Kollins SH | title = Alpha-2 adrenergic receptors and attention-deficit/hyperactivity disorder | journal = Current Psychiatry Reports | volume = 12 | issue = 5 | pages = 366–373 | date = October 2010 | pmid = 20652773 | pmc = 3676929 | doi = 10.1007/s11920-010-0136-4 }}</ref>

This mechanism is similar to the brain's physiological inhibition of PFC neurons by the [[locus ceruleus]] (LC), which secretes norepinephrine into the PFC. Although norepinephrine can also bind to target adrenergic receptors on the downstream neuron (otherwise inducing a stimulatory effect), norepinephrine also binds to α<sub>2A</sub> adrenergic receptors (akin to clonidine's mechanism of action), inhibiting the release of norepinephrine by that neuron and inducing an inhibitory effect. Because the PFC is required for working memory and attention, it is thought that clonidine's inhibition of PFC neurons helps to eliminate irrelevant attention (and subsequent behaviors), improving the person's focus and correcting deficits in attention.<ref name="Cinnamon Review" />

====Growth hormone test====
Clonidine stimulates release of [[Growth hormone–releasing hormone|GHRH hormone]] from the hypothalamus, which in turn stimulates pituitary release of [[growth hormone]].<ref name="pmid1901390">{{cite journal | vauthors = Low LC | title = Growth hormone-releasing hormone: clinical studies and therapeutic aspects | journal = Neuroendocrinology | volume = 53 | issue = Suppl 1 | pages = 37–40 | year = 1991 | pmid = 1901390 | doi = 10.1159/000125793 }}</ref> This effect has been used as part of a "growth hormone test," which can assist with diagnosing [[growth hormone deficiency]] in children.<ref name="GH Test Cinci">{{cite web |title=Growth Hormone Test |url=https://www.cincinnatichildrens.org/health/g/growth-hormone |website=www.cincinnatichildrens.org |publisher=Cincinnati Children's Hospital Medical Center |access-date=13 October 2018 |archive-date=14 October 2018 |archive-url=https://web.archive.org/web/20181014010221/https://www.cincinnatichildrens.org/health/g/growth-hormone |url-status=live }}</ref>

===Pharmacokinetics===
After being ingested, clonidine is absorbed into the blood stream rapidly with an overall [[bioavailability]] around 70–80%.<ref name="davies">{{cite journal | vauthors = Davies DS, Wing AM, Reid JL, Neill DM, Tippett P, Dollery CT | title = Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine | journal = Clinical Pharmacology and Therapeutics | volume = 21 | issue = 5 | pages = 593–601 | date = May 1977 | pmid = 870272 | doi = 10.1002/cpt1977215593 | s2cid = 5566079 }}</ref> [[Cmax (pharmacology)|Peak concentrations]] in human plasma occur within 60–90 minutes for the "immediate release" (IR) version of the drug, which is shorter than the "extended release" (ER/XR) version.<ref name="Khan Review 1999">{{cite journal | vauthors = Khan ZP, Ferguson CN, Jones RM | title = alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role | journal = Anaesthesia | volume = 54 | issue = 2 | pages = 146–165 | date = February 1999 | pmid = 10215710 | doi = 10.1046/j.1365-2044.1999.00659.x | s2cid = 28405271 | doi-access = }}</ref> Clonidine is fairly lipid soluble with the [[Partition coefficient#Partition coefficient and log P|logarithm of its partition coefficient]] (log P) equal to 1.6;<ref name="Foye 2008">{{cite book |title=Foye's principles of medicinal chemistry |url=https://archive.org/details/foyesprinciplesm00lemk |url-access=limited |date=2008 |publisher=Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-6879-5 |page=[https://archive.org/details/foyesprinciplesm00lemk/page/n2265 403] |edition= 6th }}</ref><ref name="Khan Review 1999" /> to compare, the optimal log P to allow a drug that is active in the human [[central nervous system]] to penetrate the [[blood brain barrier]] is 2.0.<ref name="Pajouhesh 2005">{{cite journal | vauthors = Pajouhesh H, Lenz GR | title = Medicinal chemical properties of successful central nervous system drugs | journal = NeuroRx | volume = 2 | issue = 4 | pages = 541–553 | date = October 2005 | pmid = 16489364 | pmc = 1201314 | doi = 10.1602/neurorx.2.4.541 }}</ref> Less than half of the absorbed portion of an orally administered dose will be metabolized by the [[liver]] into inactive [[metabolite]]s, with roughly the other half being excreted unchanged by the [[kidneys]].<ref name="Khan Review 1999" /> About one-fifth of an oral dose will not be absorbed, and is thus excreted in the feces.<ref name="Khan Review 1999" /> Work with liver microsomes shows in the liver clonidine is primarily metabolized by [[CYP2D6]] (66%), [[CYP1A2]] (10–20%), and [[CYP3A]] (0–20%) with negligible contributions from the less abundant enzymes [[CYP3A5]], [[CYP1A1]], and [[CYP3A4]].<ref name="cypmetabolism"/> 4-hydroxyclonidine, the main metabolite of clonidine, is also an α<sub>2A</sub> agonist but is non lipophilic and is not believed to contribute to the effects of clonidine since it does not cross the blood–brain barrier.<ref>{{cite journal | vauthors = Skingle M, Hayes AG, Tyers MB | title = Antinociceptive activity of clonidine in the mouse, rat and dog | journal = Life Sciences | volume = 31 | issue = 11 | pages = 1123–1132 | date = September 1982 | pmid = 6128647 | doi = 10.1016/0024-3205(82)90086-8 }}</ref><ref>{{cite journal | vauthors = Curtis AL, Marwah J | title = Alpha adrenoceptor modulation of the jaw-opening reflex | journal = Neuropharmacology | volume = 26 | issue = 7A | pages = 649–655 | date = July 1987 | pmid = 2819761 | doi = 10.1016/0028-3908(87)90224-3 | s2cid = 41743285 }}</ref>

Measurements of the [[half-life]] of clonidine vary widely, between 6 and 23 hours, with the half-life being greatly affected by and prolonged in the setting of [[kidney disease|poor kidney function]].<ref name="Khan Review 1999" /> Variations in half-life may be partially attributable to [[CYP2D6]] genetics.<ref name="cypmetabolism"/> Some research has suggested the half-life of clonidine is dose dependent and approximately doubles upon chronic dosing,<ref name="halflife">{{cite journal | vauthors = Frisk-Holmberg M, Paalzow L, Edlund PO | title = Clonidine kinetics in man--evidence for dose dependency and changed pharmacokinetics during chronic therapy | journal = British Journal of Clinical Pharmacology | volume = 12 | issue = 5 | pages = 653–658 | date = November 1981 | pmid = 7332729 | doi = 10.1111/j.1365-2125.1981.tb01284.x | pmc = 1401969 }}</ref> while other work contradicts this.<ref name = clinp/> Following a 0.3&nbsp;mg oral dose, a small study of five patients by Dollery et al. (1976) found half-lives ranging between 6.3 and 23.4 hours ([[mean]] 12.7).<ref>{{cite journal | vauthors = Dollery CT, Davies DS, Draffan GH, Dargie HJ, Dean CR, Reid JL, Clare RA, Murray S | title = Clinical pharmacology and pharmacokinetics of clonidine | journal = Clinical Pharmacology and Therapeutics | volume = 19 | issue = 1 | pages = 11–17 | date = January 1976 | pmid = 1245090 | doi = 10.1002/cpt197619111 | s2cid = 39473828 }}</ref> A similar N=5 study by Davies et al. (1977) found a narrower range of half-lives, between 6.7 and 13 hours (mean 8.6),<ref name="davies"/> while an N=8 study by Keraäen et al. that included younger patients found a somewhat shorter mean half-life of 7.5 hours.<ref>{{cite journal | vauthors = Keränen A, Nykänen S, Taskinen J | title = Pharmacokinetics and side-effects of clonidine | journal = European Journal of Clinical Pharmacology | volume = 13 | issue = 2 | pages = 97–101 | date = May 1978 | pmid = 658114 | doi = 10.1007/BF00609752 | s2cid = 24702183 }}</ref>

==History==
Clonidine was introduced in 1966.<ref name="history1">{{cite journal | vauthors = Stähle H | title = A historical perspective: development of clonidine | journal = Best Practice & Research Clinical Anaesthesiology | date = June 2000 | volume = 14 | issue = 2 | pages = 237–246 | doi = 10.1053/bean.2000.0079 }}</ref> It was first used as a hypertension treatment under the trade name of Catapres.<ref>{{Cite web|url=https://www.drugs.com/clonidine.html|title=Clonidine: Drug Uses, Dosage & Side Effects - Drugs.com|work=Drugs.com|access-date=10 December 2017|archive-date=14 April 2017|archive-url=https://web.archive.org/web/20170414001745/https://www.drugs.com/clonidine.html|url-status=live}}</ref>

==Society and culture==

===Brand names===
As of June 2017, clonidine is marketed under many brand names worldwide: Arkamin, Aruclonin, Atensina, Catapin, Catapres, Catapresan, Catapressan, Chianda, Chlofazoline, Chlophazolin, Clonid-Ophtal, Clonidin, Clonidina, Clonidinã, Clonidine, Clonidine hydrochloride, Clonidinhydrochlorid, Clonidini, Clonidinum, Clonigen, Clonistada, Clonnirit, Clophelinum, Dixarit, Duraclon, Edolglau, Haemiton, Hypodine, Hypolax, Iporel, Isoglaucon, Jenloga, Kapvay, Klofelino, Kochaniin, Lonid, Melzin, Menograine, Normopresan, Paracefan, Pinsanidine, Run Rui, and Winpress.<ref name=brands>{{cite web|title=Clonidine brand names|url=https://www.drugs.com/international/clonidine.html|publisher=Drugs.com|access-date=16 June 2017|archive-date=6 August 2017|archive-url=https://web.archive.org/web/20170806101340/https://www.drugs.com/international/clonidine.html|url-status=live}}</ref> It is marketed as a [[combination drug]] with [[chlortalidone]] as Arkamin-H, Bemplas, Catapres-DIU, and Clorpres, and in combination with [[bendroflumethiazide]] as Pertenso.<ref name=brands/>

== References ==
{{Reflist}}

== External links ==
{{Commons category}}
* Alpha-2 agonists in [http://www.medscape.org/viewarticle/560074 ADHD]

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