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an antihypertensive (trade name Catapres) that can be administered orally or via transdermal patches (同)Catapres

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/02 04:06:01」(JST)

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Clonidine (trade names Catapres, Kapvay, Nexiclon, Clophelin, and others) is a medication used to treat high blood pressure, attention deficit hyperactivity disorder, anxiety disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions.^[4] It is classified as a centrally acting α₂ adrenergic agonist and imidazoline receptor agonist that has been in clinical use for over 40 years.^[5]

Medical uses

Clonidine tablets and transdermal patch

The US Food and Drug Administration (FDA) has approved clonidine for the treatment of attention deficit hyperactivity disorder (ADHD), alone or with stimulants in 2010, for pediatric patients aged 6–17 years.^[2]^[6] It was later approved for adults. In Australia, clonidine is an accepted but not approved use for ADHD by the TGA.^[7] Clonidine along with methylphenidate has been studied for treatment of ADHD.^[8]^[9]^[10] Some studies show clonidine more sedating than guanfacine, which may be better at bed time along with an arousing stimulant at morning.^[11]^[12] Clonidine can be used in the treatment of Tourette syndrome (specifically for tics).^[13] Clonidine may be used to ease withdrawal symptoms associated with the long-term use of narcotics, alcohol, benzodiazepine and nicotine (smoking).^[14] 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.^[15] It may also be helpful in aiding smokers to quit.^[16] The sedation effect is also useful although its side effects can include insomnia, thus exacerbating an already common feature of opioid withdrawal.^[17]

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.^[18]^[19]^[20]^[21]^[22]^[23]^[24]^[25] Clonidine is also a mild sedative, and can be used as premedication before surgery or procedures.^[26] Its epidural use for pain during heart attack, postoperative and intractable pain has also been studied extensively.^[27] Clonidine has also been suggested as a treatment for rare instances of dexmedetomidine withdrawal.^[28] Clonidine can be used in restless legs syndrome. It can also be used to treat facial flushing and redness associated with rosacea.^[29] It has also been successfully used topically in a clinical trial as a treatment for diabetic neuropathy.^[30] Clonidine can also be used for migraine headaches and hot flashes associated with menopause.^[31]^[32]

Clonidine suppression test

Clonidine's effect on reducing circulating epinephrine by a central mechanism was used in the past as an investigatory test for phaeochromocytoma, which is a catecholamine-synthesizing tumour, usually of the adrenal medulla.^[33] 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 somebody. A positive test occurs if there is no decrease in plasma levels.^[33]

Pregnancy

Clonidine is classed by the FDA as pregnancy category C. It is classified by the TGA of Australia 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.^[34] Clonidine can pass into breast milk and may harm a nursing baby; caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.^[35]

Adverse effects

The principle adverse effects of clonidine are sedation, dry mouth, and hypotension (low blood pressure).^[2]

Adverse effects by frequency^[34]^[36]^[37]

Very common (>10% frequency):

Dizziness
Drops in blood pressure upon standing up
Somnolence (drowsiness; dose-dependent)
Dry mouth
Headache (dose-dependent)
Fatigue
Skin reactions (if given transdermally)
Low blood pressure

Common (1-10% frequency):

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% frequency):

Delusional perception
Hallucination
Nightmare
Paraesthesia
Sinus bradycardia
Raynaud's phenomenon
Itchiness
Hives

Rare (<0.1% frequency):

Swelling of breast tissue in males
Impaired ability to cry
Atrioventricular block
Nasal dryness
Colonic pseudo-obstruction
Alopecia (hair loss)
High blood sugar

Withdrawal

Clonidine suppresses sympathetic outflow resulting in lower blood pressure, but sudden discontinuation can cause rebound hypertension due to a rebound in sympathetic outflow.^[4]

Clonidine therapy should generally be gradually tapered 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.^[38]^[39]

Mechanism of action

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.^[40] 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.^[41] Its mechanism of action in the treatment of ADHD is to increase noradrenergic tone in the prefrontal cortex (PFC) directly by binding to postsynaptic α_2A adrenergic receptors and indirectly by increasing norepinephrine input from the locus coeruleus.^[42]

Receptor	K_i (nM)^[43]
α_1A	316.23
α_1B	316.23
α_1D	125.89
α_2A	42.92
α_2B	106.31
α_2C	233.1

References

^ ^a ^b Lowenthal, DT; Matzek, KM; MacGregor, TR (May 1988). "Clinical pharmacokinetics of clonidine.". Clinical Pharmacokinetics 14 (5): 287–310. doi:10.2165/00003088-198814050-00002. PMID 3293868.
^ ^a ^b ^c ^d ^e "clonidine (Rx) - Catapres, Catapres-TTS, more..". Medscape Reference. WebMD. Retrieved 10 November 2013.
^ [1]
^ ^a ^b Brayfield, A, ed. (13 January 2014). "Clonidine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 28 June 2014.
^ Neil, MJ (November 2011). "Clonidine: clinical pharmacology and therapeutic use in pain management.". Current Clinical Pharmacology 6 (4): 280–7. doi:10.2174/157488411798375886. PMID 21827389.
^ "FDA Approves Extended-Release Clonidine for Pediatric ADHD". WebMD LLC.
^ Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
^ Palumbo, DR; Sallee, FR; Pelham WE, Jr; Bukstein, OG; Daviss, WB; McDermott, MP (February 2008). "Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes.". Journal of the American Academy of Child and Adolescent Psychiatry 47 (2): 180–8. doi:10.1097/chi.0b013e31815d9af7. PMID 18182963.
^ Daviss, WB; Patel, NC; Robb, AS; McDermott, MP; Bukstein, OG; Pelham WE, Jr; Palumbo, D; Harris, P; Sallee, FR (February 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): 189–98. doi:10.1097/chi.0b013e31815d9ae4. PMID 18182964.
^ 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/appi.ps.201200147. PMC 4023684. PMID 23318985.
^ "Guanfacine, But Not Clonidine, Improves Planning and Working Memory Performance in Humans". Neuropsychopharmacology. Retrieved August 2014.
^ "Clonidine and Guanfacine IR vs ER: Old Drugs With "New" Formulations". Mental Health Clinician. Retrieved August 2014.
^ Egolf, A; Coffey, BJ (February 2014). "Current pharmacotherapeutic approaches for the treatment of Tourette syndrome.". Drugs of Today 50 (2): 159–79. doi:10.1358/dot.2014.50.2.2097801. PMID 24619591.
^ Fitzgerald, PJ (October 2013). "Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine.". Substance Abuse 7: 171–83. doi:10.4137/SART.S13019. PMC 3798293. PMID 24151426.
^ Giannini, AJ (1997). Drugs of Abuse (2nd ed.). Los Angeles: Practice Management Information.
^ Gourlay, SG; Stead, LF; Benowitz, NL (2004). "Clonidine for smoking cessation.". The Cochrane Database of Systematic Reviews (3): CD000058. doi:10.1002/14651858.CD000058.pub2. PMID 15266422.
^ Giannini, AJ; Extein, I; Gold, MS; Pottash, ALC; Castellani, S (1983). "Clonidine in mania". Drug Development Research 3 (1): 101–105. doi:10.1002/ddr.430030112.
^ van der Kolk, BA (September–October 1987). "The drug treatment of post-traumatic stress disorder.". Journal of Affective Disorders 13 (2): 203–13. doi:10.1016/0165-0327(87)90024-3. PMID 2960712.
^ Sutherland, SM; Davidson, JR (June 1994). "Pharmacotherapy for post-traumatic stress disorder.". The Psychiatric Clinics of North America 17 (2): 409–23. PMID 7937367.
^ Southwick, SM; Bremner, JD; Rasmusson, A; Morgan CA, 3rd; Arnsten, A; Charney, DS (November 1999). "Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder.". Biological Psychiatry 46 (9): 1192–204. doi:10.1016/S0006-3223(99)00219-X. PMID 10560025.
^ Strawn, JR; Geracioti, TD, Jr (2008). "Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder.". Depression and Anxiety 25 (3): 260–71. doi:10.1002/da.20292. PMID 17354267.
^ Boehnlein, JK; Kinzie, JD (March 2007). "Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin.". Journal of Psychiatric Practice 13 (2): 72–8. doi:10.1097/01.pra.0000265763.79753.c1. PMID 17414682.
^ Huffman, JC; Stern, TA (2007). "Neuropsychiatric consequences of cardiovascular medications.". Dialogues in Clinical Neuroscience 9 (1): 29–45. PMC 3181843. PMID 17506224.
^ Najjar, F; Weller, RA; Weisbrot, J; Weller, EB (April 2008). "Post-traumatic stress disorder and its treatment in children and adolescents.". Current Psychiatry Reports 10 (2): 104–8. doi:10.1007/s11920-008-0019-0. PMID 18474199.
^ Ziegenhorn, AA; Roepke, S; Schommer, NC; Merkl, A; Danker-Hopfe, H; Perschel, FH; Heuser, I; Anghelescu, IG; Lammers, CH (April 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): 170–3. doi:10.1097/JCP.0b013e31819a4bae. PMID 19512980.
^ Fazi, L; Jantzen, EC; Rose, JB; Kurth, CD; Watcha, MF (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. doi:10.1097/00000539-200101000-00011. PMID 11133600.
^ Patel, SS; Dunn, CJ; Bryson, HM (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.
^ Kukoyi, AT; Coker, SA; Lewis, LD; Nierenberg, DW (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.
^ Blount, BW; Pelletier, AL (2002). "Rosacea: A Common, Yet Commonly Overlooked, Condition". American Family Physician 66 (3): 435–441. PMID 12182520.
^ 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.
^ "Clonidine Oral Uses". WebMD.
^ "Clonidine". Drugs.com.
^ ^a ^b Eisenhofer, G; Goldstein, DS; Walther, MM; et al. (2003). "Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results". Journal of Clinical Endocrinology & Metabolism 88 (6): 2656–2666. doi:10.1210/jc.2002-030005. PMID 12788870.
^ ^a ^b "CATAPRES® 150 TABLETS CATAPRES® AMPOULES" (PDF). TGA eBusiness Services. Boehringer Ingelheim Pty Limited. 28 February 2013. Retrieved 27 November 2013.
^ "Clonidine". Prescription Marketed Drugs. www.drugsdb.eu.
^ "CATAPRES (clonidine hydrochloride) tablet [Boehringer Ingelheim Pharmaceuticals Inc.]". DailyMed. Boehringer Ingelheim Pharmaceuticals Inc. June 2012. Retrieved 27 November 2013.
^ "Clonidine 25 mcg Tablets BP - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sandoz Limited. 2 August 2012. Retrieved 27 November 2013.
^ Parker, K; Brunton, L; Goodman, LS; Lazo, JS; Gilman, A (2006). Goodman & Gilman's - the pharmacological basis of therapeutics. New York: McGraw-Hill. pp. 854–855. ISBN 0-07-142280-3.
^ 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.
^ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 12. ISBN 1-59541-101-1.
^ 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.
^ Sallee, FR (2008). "The Role of Alpha 2 Agonists in the Attention Deficit/Hyperactivity Disorder Treatment Paradigm". Medscape Reference. WebMD. Retrieved 15 November 2013.
^ Roth, BL; Driscol, J (12 January 2011). "PDSP K_i 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.

External links

U.S. National Library of Medicine: Drug Information Portal - Clonidine
Alpha-2 agonists in ADHD

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. クロニジンおよびイミダゾリンによる中毒 clonidine and related imidazoline poisoning
2. 思春期におけるオピオイド離脱 opioid withdrawal in adolescents
3. Complex regional pain syndrome in adults: Prevention and management
4. 降圧療法に伴う離脱症候群 withdrawal syndromes with antihypertensive therapy
5. Spinal anesthesia: Technique

English Journal

Modulation of fear/anxiety responses, but not food intake, following α-adrenoceptor agonist microinjections in the nucleus accumbens shell of free-feeding rats.

Kochenborger L, Zanatta D, Berretta LM, Lopes AP, Wunderlich BL, Januário AC, Neto JM, Terenzi MG, Paschoalini MA, Faria MS.SourceDepartment of Physiological Sciences, Centre of Biological Sciences, Federal University of Santa Catarina (UFSC), 88040-900 Florianópolis, SC, Brazil. larissakochen@gmail.com
Neuropharmacology.Neuropharmacology.2012 Jan;62(1):427-35. Epub 2011 Aug 18.
This study investigated the effect of α-adrenoceptor agonists microinjected into the shell region of the accumbens nucleus (AcbSh) on feeding and anxiety-related behaviors in free-feeding rats. Male Wistar rats with a chronically implanted cannula into the AcbSh were unilaterally microinjected with
PMID 21871465

Pharmacological reversal of cognitive bias in the chick anxiety-depression model.

Hymel KA, Sufka KJ.SourceDepartment of Psychology, University of Mississippi, Oxford, MS 38677, USA. Kahyme@olemiss.edu
Neuropharmacology.Neuropharmacology.2012 Jan;62(1):161-6. Epub 2011 Jun 23.
Cognitive bias presents in clinical populations where anxious individuals adopt a more pessimistic interpretation of ambiguous aversive stimuli and depressed individuals adopt both a more pessimistic interpretation of ambiguous aversive stimuli and a less optimistic interpretation of ambiguous appet
PMID 21722654

Japanese Journal

HPLC-UV method development for fentanyl determination in rat plasma and its application to elucidate pharmacokinetic behavior after i.p. administration to rats.

Almousa Ahmed A,Ikeda Rie,Wada Mitsuhiro,Kuroda Naotoka,Hanajiri Ruri-Kikura,Nakashima Kenichiro
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 879(27), 2941-2944, 2011-10-01
… Plasma sample (100 μL) pretreatment was based on simple deprotienization by acetonitrile spiked with clonidine as an internal standard (I.S.) of 20 ng/mL followed by extraction with tert-butyl methyl ether and centrifugation. …
NAID 120003477533

ヨヒンビン投与卵巣摘出ラットにおけるホットフラッシュ様症状に対するエストロゲン及び桂枝茯苓丸の作用

森元康夫,青塚保志,柴田裕次郎
YAKUGAKU ZASSHI 131(8), 1241-1250, 2011
… We next examined the effects of various drugs, which are clinically effective against postmenopausal HF, on HF-like symptoms in YOH-treated OVX rats: clonidine, a presynaptic α2-adrenoceptor agonist which inhibits norepinephrine release; …
NAID 130001075914

Related Pictures

★リンクテーブル★

リンク元	「クロニジン」
拡張検索	「apraclonidine hydrochloride」「clonidine hydrochloride」

「クロニジン」

Clonidine
Systematic (IUPAC) name
	N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine
Clinical data
Trade names	Catapres, Kapvay, Nexiclon
AHFS/Drugs.com	monograph
MedlinePlus	a682243
Licence data	US FDA:link
Pregnancy; category	AU: B3; US: C (Risk not ruled out); ;
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Routes of; administration	oral, epidural, IV, transdermal, topical
Pharmacokinetic data
Bioavailability	75-95% (oral), 60-70% (transdermal)
Protein binding	20-40%
Metabolism	Hepatic to inactive metabolites, 2/3 CYP2D6 [2]
Biological half-life	IR: 12-16 hours, 14 hours for repeated dosing
Excretion	urine (72%)
Identifiers
CAS Number	4205-90-7
ATC code	C02AC01 N02CX02, S01EA04
PubChem	CID: 2803
IUPHAR/BPS	516
DrugBank	DB00575
ChemSpider	2701
UNII	MN3L5RMN02
KEGG	D00281
ChEBI	CHEBI:3757
ChEMBL	CHEMBL134
Chemical data
Formula	C9H9Cl2N3
Molecular mass	230.093 g/mol
	SMILES Clc1c(c(Cl)ccc1)N/C2=N/CCN2 ;
	InChI 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) ; Key:GJSURZIOUXUGAL-UHFFFAOYSA-N ;
(verify)

　　[★]

英: clonidine
商: Catapres、カタプレス
化: 塩酸クロニジン

α₂受容体のアゴニスト
中枢性交感神経抑制薬
抗高血圧薬として使われる
中枢性に降圧作用を生じる

薬理作用 (SPC.251)

脳幹部のα₂受容体を刺激し、末梢交感神経活性を遮断

α₂受容体はシナプス前膜上に存在して抑制性に働く

「apraclonidine hydrochloride」

　　[★]

塩酸アプラクロニジン

関: apraclonidine

「clonidine hydrochloride」

　　[★]

塩酸クロニジン

関: clonidine

[clinp-1] Lowenthal, DT; Matzek, KM; MacGregor, TR (May 1988). "Clinical pharmacokinetics of clonidine.". Clinical Pharmacokinetics 14 (5): 287–310. doi:10.2165/00003088-198814050-00002. PMID 3293868.

[MSR-2] "clonidine (Rx) - Catapres, Catapres-TTS, more..". Medscape Reference. WebMD. Retrieved 10 November 2013.

[3] [1]

[MD-4] Brayfield, A, ed. (13 January 2014). "Clonidine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 28 June 2014.

[5] Neil, MJ (November 2011). "Clonidine: clinical pharmacology and therapeutic use in pain management.". Current Clinical Pharmacology 6 (4): 280–7. doi:10.2174/157488411798375886. PMID 21827389.

[6] "FDA Approves Extended-Release Clonidine for Pediatric ADHD". WebMD LLC.

[AMH-7] Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.

[8] Palumbo, DR; Sallee, FR; Pelham WE, Jr; Bukstein, OG; Daviss, WB; McDermott, MP (February 2008). "Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes.". Journal of the American Academy of Child and Adolescent Psychiatry 47 (2): 180–8. doi:10.1097/chi.0b013e31815d9af7. PMID 18182963.

[9] Daviss, WB; Patel, NC; Robb, AS; McDermott, MP; Bukstein, OG; Pelham WE, Jr; Palumbo, D; Harris, P; Sallee, FR (February 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): 189–98. doi:10.1097/chi.0b013e31815d9ae4. PMID 18182964.

[Effects-10] 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/appi.ps.201200147. PMC 4023684. PMID 23318985.

[11] "Guanfacine, But Not Clonidine, Improves Planning and Working Memory Performance in Humans". Neuropsychopharmacology. Retrieved August 2014.

[12] "Clonidine and Guanfacine IR vs ER: Old Drugs With "New" Formulations". Mental Health Clinician. Retrieved August 2014.

[13] Egolf, A; Coffey, BJ (February 2014). "Current pharmacotherapeutic approaches for the treatment of Tourette syndrome.". Drugs of Today 50 (2): 159–79. doi:10.1358/dot.2014.50.2.2097801. PMID 24619591.

[14] Fitzgerald, PJ (October 2013). "Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine.". Substance Abuse 7: 171–83. doi:10.4137/SART.S13019. PMC 3798293. PMID 24151426.

[15] Giannini, AJ (1997). Drugs of Abuse (2nd ed.). Los Angeles: Practice Management Information.

[16] Gourlay, SG; Stead, LF; Benowitz, NL (2004). "Clonidine for smoking cessation.". The Cochrane Database of Systematic Reviews (3): CD000058. doi:10.1002/14651858.CD000058.pub2. PMID 15266422.

[17] Giannini, AJ; Extein, I; Gold, MS; Pottash, ALC; Castellani, S (1983). "Clonidine in mania". Drug Development Research 3 (1): 101–105. doi:10.1002/ddr.430030112.

[18] van der Kolk, BA (September–October 1987). "The drug treatment of post-traumatic stress disorder.". Journal of Affective Disorders 13 (2): 203–13. doi:10.1016/0165-0327(87)90024-3. PMID 2960712.

[19] Sutherland, SM; Davidson, JR (June 1994). "Pharmacotherapy for post-traumatic stress disorder.". The Psychiatric Clinics of North America 17 (2): 409–23. PMID 7937367.

[20] Southwick, SM; Bremner, JD; Rasmusson, A; Morgan CA, 3rd; Arnsten, A; Charney, DS (November 1999). "Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder.". Biological Psychiatry 46 (9): 1192–204. doi:10.1016/S0006-3223(99)00219-X. PMID 10560025.

[21] Strawn, JR; Geracioti, TD, Jr (2008). "Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder.". Depression and Anxiety 25 (3): 260–71. doi:10.1002/da.20292. PMID 17354267.

[22] Boehnlein, JK; Kinzie, JD (March 2007). "Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin.". Journal of Psychiatric Practice 13 (2): 72–8. doi:10.1097/01.pra.0000265763.79753.c1. PMID 17414682.

[23] Huffman, JC; Stern, TA (2007). "Neuropsychiatric consequences of cardiovascular medications.". Dialogues in Clinical Neuroscience 9 (1): 29–45. PMC 3181843. PMID 17506224.

[24] Najjar, F; Weller, RA; Weisbrot, J; Weller, EB (April 2008). "Post-traumatic stress disorder and its treatment in children and adolescents.". Current Psychiatry Reports 10 (2): 104–8. doi:10.1007/s11920-008-0019-0. PMID 18474199.

[25] Ziegenhorn, AA; Roepke, S; Schommer, NC; Merkl, A; Danker-Hopfe, H; Perschel, FH; Heuser, I; Anghelescu, IG; Lammers, CH (April 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): 170–3. doi:10.1097/JCP.0b013e31819a4bae. PMID 19512980.

[premed-26] Fazi, L; Jantzen, EC; Rose, JB; Kurth, CD; Watcha, MF (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. doi:10.1097/00000539-200101000-00011. PMID 11133600.

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