塩酸グアンファシン

関: guanfacine

WordNet

a complex consisting of an organic base in association with hydrogen chloride

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/03 20:52:28」(JST)

wiki en

Not to be confused with Guanine, Guanosine, Guanidine, or Guaifenesin.

Guanfacine (brand name Tenex, and the extended release Intuniv) is a sympatholytic. It is a selective α_2A receptor agonist. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α_2A receptors in the prefrontal cortex.^[1] Guanfacine lowers both systolic and diastolic blood pressure by activating the central nervous system α-2a norepinephrine autoreceptors, which results in reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone.^[2] Its side-effects are dose dependent, with practically no dryness of the mouth at doses of 2 mg and less.^[3]

Medical Uses

Hypertension

It reduces hypertension not just in short-term, but also as shown in long-term studies with normalization of blood pressure of 54% treated over a year and 66% over two years.^[4]

1 mg Guanfacine tablets.

Attention-deficit hyperactivity disorder

An extended-release formulation of guanfacine (Intuniv) has also been approved by the FDA for the treatment of attention-deficit hyperactivity disorder (ADHD) in people ages 6-17. Its beneficial actions are likely due to its ability to strengthen prefrontal cortical regulation of attention and behavior.^[5] Guanfacine is also used in conjunction with stimulants to augment therapeutic actions, counter side effects, reduce rebound, and when taken at night, to induce sleep.^[6] Guanfacine is thought to improve regulation of behavior, attention, and emotion through actions at post-synaptic alpha-2A adrenergic receptors on prefrontal cortical neurons, which strengthen prefrontal cortical network connections.^[7] In animal models, guanfacine is seen to affect a number of cognitive factors, including working memory improvement, distractibility reduction, response inhibition improvement, and attention control.^[5] Performance increases in spatial working memory have also been observed in humans.^[8] Another study found no effect on healthy male adults' executive functions and working memory, and small decrements on 2 tasks relating to the sedative effect of guanfacine.^[9]

Anxiety

Another psychiatric use of guanfacine is for treatment of anxiety, such as generalized anxiety disorder and post-traumatic stress disorder symptoms. Guanfacine and other alpha-2A agonist reduce sympathetic arousal, weaken the emotional responses of the amygdala, and strengthen prefrontal cortical regulation of emotion, action and thought. All of these actions likely contribute to the relief of the hyperarousal, re-experiencing of memory, and impulsivity associated with PTSD.^[10] Due to its prolonged half-life, it also has been seen to improve sleep interrupted by nightmares in PTSD patients.^[11]

Tics

According to recent studies (Srour et al., 2008) there is controversy as to guanfacine’s usefulness in treating tics. There has been success when tic symptoms are co-morbid with ADHD, and as such, guanfacine and other alpha-2-adrenergic agonists (clonidine) are commonly the first choice for treatment.

http://news.healingwell.com/index.php?p=news1&id=536351

Withdrawal

Guanfacine is also being investigated for treatment of withdrawal for opioids, alcohol, and nicotine.^[12]

Side effects

Usual: dizziness, drowsiness, headache, depression, constipation, gas pains, diarrhea, loss of appetite, fatigue, and nasal congestion may occur.^[13]

Rare: chest pain, shortness of breath, skin rash, swelling of the hands or feet, blurred vision, yellowing of the eyes or skin.

Others: mental/mood changes, tingling of the hands or feet, dry mouth, impotence, decreased sexual desire, vision changes, taste changes, ringing in the ears, leg cramps.^[14]

Cardiovascular side effects include orthostatic hypotension, dizziness, palpitations, and tachycardia upon standing, and possibly bradycardia. Rebound hypertension is a possibility with abrupt discontinuation, and as such a gradual discontinuation is recommended.^[15]

Interactions

CYP3A4/5 inhibitors — Use caution. Elevates plasma concentration of guanfacine.
CYP3A4 inducers — Recommended increase in guanfacine dose.
Valproic acid — Use caution. Elevates plasma concentration of valproic acid.
Antihypertensive drugs — Use caution. Potential for additive pharmacodynamic effects (hypotension, syncope, etc.)
CNS depressant drugs — Use caution. Potential for additive pharmacodynamic effects (sedation, somnolence, etc.)

Pharmacokinetics and metabolism

Guanfacine shows an absolute bioavailability of nearly 100%. There is no clear evidence of any first-pass metabolism. Elimination half-life is 17 hours with the major elimination route being renal. The principal metabolite is the 3-hydroxy derivative, with evidence of moderate biotransformation, and the key intermediate being an epoxide.^[16] It is also shown that elimination in patients with impaired renal function does not differ significantly from those with normal renal function. As such, metabolism by liver is the assumption for those with impaired renal function, as supported by increased frequency of known side effects of orthostatic hypotension and sedation.^[17] In animal models, guanfacine’s enhancing effects on the working-memory functions of the pre-frontal cortex are thought to be due to inhibition of cAMP-mediated signaling, which is effected by the Gi proteins that are generally coupled to the post-synaptic alpha-2a-adrenoceptors that guanfacine stimulates through binding.^[18]

Notes and references

^ Kolar, Dusan; Keller, Amanda; Golfinopoulos, Maria; Cumyn, Lucy; Syer, Cassidy & Hechtman, Lily (2008), "Treatment of adults with attention-deficit/hyperactivity disorder", Neuropsychiatric Disease and Treatment 4 (2): 389–403, PMC 2518387, PMID 18728745 .
^ Van Zwieten, P.; Thoolen, M. & Timmermans, P. (1983), "The pharmacology of centrally acting antihypertensive drugs", British Journal of Clinical Pharmacology 15 (Suppl 4): 455S–462S, PMC 1427667 .
^ Jerie, P. (1980), "Clinical experience with guanfacine in long-term treatment of hypertension: Part II: adverse reactions to guanfacine", British Journal of Clinical Pharmacology 10 (Suppl 1): 157S–164S, PMC 1430125, PMID 6994770 .
^ Jerie, P. (1980), "Clinical experience with guanfacine in long-term treatment of hypertension: Part I: efficacy and dosage", British Journal of Clinical Pharmacology 10 (Suppl 1): 37S–47S, PMC 1430120, PMID 6994777 .
^ ^a ^b Arnsten AF. The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 10:1595-605, 2010
^ Zito, Julie M.; Derivan, Albert T.; Kratochvil, Christopher J.; et al., DJ; Fegert, JM; Greenhill, LL (2008), "Off-label psychopharmacologic prescribing for children: History supports close clinical monitoring", Child and Adolescent Psychiatry and Mental Health 2 (1): 24, doi:10.1186/1753-2000-2-24, PMC 2566553, PMID 18793403
^ Wang, M; Ramos, BP (2007), "Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex", Cell 129 (2): 397–410, doi:10.1016/j.cell.2007.03.015, PMID 17448997
^ Jäkälä P, Riekkinen M, Sirviö J, Koivisto E, Kejonen K, Vanhanen M, Riekkinen P Jr. Guanfacine, but not clonidine, improves planning and working memory performance in humans. Neuropsychopharmacology. 20:460-70, 1999.
^ Müller, U; Clark, L; Lam, ML; Moore, RM; Murphy, CL; Richmond, NK; Sandhu, RS; Wilkins, IA et al. (2005), "Lack of effects of guanfacine on executive and memory functions in healthy male volunteers", Psychopharmacology 182 (2): 205–13, doi:10.1007/s00213-005-0078-4, PMID 16078088.
^ Kaminer, D.; Seedat, S. & Stein, D. (2005), "Post-traumatic stress disorder in children", World Psychiatry 4 (2): 121–125, PMC 1414752, PMID 16633528 .
^ Kozarlc-Kovaclc, D. (2008), "Psychopharmacotherapy of Posttraumatic Stress Disorder", Croatian Medical Journal 49 (4): 459–475, doi:10.3325/cmj.2008.4.459, PMC 2525822, PMID 18716993 .
^ Sofuogul, M. & Sewell, A. (2009), "Norepinephrine and Stimulant Addiction", Addiction Biology 14 (2): 119–129, doi:10.1111/j.1369-1600.2008.00138.x, PMC 2657197, PMID 18811678
^ "Intuniv for ADHD: Efficacy, Side Effects". Health and Life. http://healthlifeandstuff.com/2009/09/intuniv-for-adhd-concerns-efficacy/.
^ "ADHD Drugs and Side Effects in Children". http://health.ltgovernors.com/mental-health/adhd-drugs-and-side-effects-in-children.html.
^ Vitiello B (April 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): 459–74, xi, doi:10.1016/j.chc.2007.11.010, PMC 2408826, PMID 18295156.
^ Kiechel, J. (1980), "Pharmacokinetics and metabolism of guanfacine in man: A review", British Journal of Clinical Pharmacology 10 (Suppl 1): 25S–32S, PMC 1430131, PMID 6994775 .
^ Kirch, W.; Kohler, H. & Braun, W. (1980), "Elimination of guanfacine in patients with normal and impaired renal function", British Journal of Clinical Pharmacology 10 (Suppl 1): 33S–35S, PMC 1430110, PMID 6994776 .
^ Ramos, Brian P.; Stark, David; Verduzco, Luis; van Dyck, Christopher H.; Arnsten, Amy F. T. (2006), "α2A-adrenoceptor stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals", Learning & Memory 13 (6): 770–776, doi:10.1101/lm.298006, PMC 1783631, PMID 17101879 .

External links

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UpToDate Contents

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1. 小児および思春期における注意欠陥多動性障害治療薬の薬理学 pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents
2. 成人の注意欠陥多動性障害（ADHD）に対する薬物療法 pharmacotherapy for adult attention deficit hyperactivity disorder
3. 小児および思春期における注意欠陥多動性障害：薬物治療 attention deficit hyperactivity disorder in children and adolescents treatment with medications
4. クロニジンおよびイミダゾリンによる中毒 clonidine and related imidazoline poisoning
5. 小児および思春期における自閉症スペクトラム障害：薬理学的介入 autism spectrum disorder in children and adolescents pharmacologic interventions

English Journal

A HPLC-MS method to detect and quantify guanfacine in urine.

Wolf CE, Kester-Florin SJ, Poklis A.SourceDepartment of Forensic Science, Virginia Commonwealth University, Richmond, VA, USA.
Clinical chemistry and laboratory medicine : CCLM / FESCC.Clin Chem Lab Med.2011 Nov 24. [Epub ahead of print]
Abstract Background: Guanfacine, an α2-adrenergic α(2A)) agonist long indicated to treat hypertension, is now being used to treat attention deficit-hyperactivity disorder (ADHD) in adolescents. This new therapeutic use may require urine testing to document compliance or abuse. A simple rapid hig
PMID 22112053

Dried blood spots as a sampling technique for the quantitative determination of guanfacine in clinical studies.

Li Y, Henion J, Abbott R, Wang P.SourceAdvion BioServices, Inc., Ithaca, NY, USA.
Bioanalysis.Bioanalysis.2011 Nov;3(22):2501-14.
Background: Dried blood spot (DBS) technology was evaluated for the quantitative determination of guanfacine in human blood in clinical studies. A very sensitive DBS assay has been developed using HPLC coupled with an AB Sciex 5500 QTRAP(®) (Applied Biosystems/MDS Sciex, ON, Canada) MS system (LC-M
PMID 22122599

Japanese Journal

Electroencephalographic and psychometric assessment of the CNS effects of single doses of guanfacine hydrochloride (Estulic) and clonidine (Catapres)

YAMADERA H.
Neuropsychobiology 14, 97-107, 1985
NAID 10009554839

「グアンファシン」

Guanfacine
Systematic (IUPAC) name
	N-(diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide
Clinical data
Trade names	Tenex, Intuniv
AHFS/Drugs.com	monograph
MedlinePlus	a601059
Pregnancy cat.	B
Legal status	℞ Prescription only
Routes	oral, intravenous
Pharmacokinetic data
Bioavailability	99.9%
Metabolism	CYP3A4
Half-life	14.8–18.3 h
Excretion	renal
Identifiers
CAS number	29110-47-2
ATC code	C02AC02
PubChem	CID 3519
IUPHAR ligand	522
DrugBank	DB01018
ChemSpider	3399
UNII	30OMY4G3MK
KEGG	D08031
ChEMBL	CHEMBL862
Chemical data
Formula	C9H9Cl2N3O
Mol. mass	246.093 g/mol
	SMILES Clc1cccc(Cl)c1CC(=O)\N=C(/N)N;
	InChI InChI=1S/C9H9Cl2N3O/c10-6-2-1-3-7(11)5(6)4-8(15)14-9(12)13/h1-3H,4H2,(H4,12,13,14,15) ; Key:INJOMKTZOLKMBF-UHFFFAOYSA-N ;
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　　[★]

英: guanfacine
化: 塩酸グアンファシン guanfacine hydrochloride guanfacine HCl
商: エスタリック, Tenex
関: グァンファシン

「グァンファシン」

　　[★]

英: guanfacine、guanfacine hydrochloride
関: グアンファシン、塩酸グアンファシン

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[Kolar-0] Kolar, Dusan; Keller, Amanda; Golfinopoulos, Maria; Cumyn, Lucy; Syer, Cassidy & Hechtman, Lily (2008), "Treatment of adults with attention-deficit/hyperactivity disorder", Neuropsychiatric Disease and Treatment 4 (2): 389–403, PMC 2518387, PMID 18728745 .

[1] Van Zwieten, P.; Thoolen, M. & Timmermans, P. (1983), "The pharmacology of centrally acting antihypertensive drugs", British Journal of Clinical Pharmacology 15 (Suppl 4): 455S–462S, PMC 1427667 .

[Jerie-2] Jerie, P. (1980), "Clinical experience with guanfacine in long-term treatment of hypertension: Part II: adverse reactions to guanfacine", British Journal of Clinical Pharmacology 10 (Suppl 1): 157S–164S, PMC 1430125, PMID 6994770 .

[3] Jerie, P. (1980), "Clinical experience with guanfacine in long-term treatment of hypertension: Part I: efficacy and dosage", British Journal of Clinical Pharmacology 10 (Suppl 1): 37S–47S, PMC 1430120, PMID 6994777 .

[Arnsten-4] Arnsten AF. The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 10:1595-605, 2010

[5] Zito, Julie M.; Derivan, Albert T.; Kratochvil, Christopher J.; et al., DJ; Fegert, JM; Greenhill, LL (2008), "Off-label psychopharmacologic prescribing for children: History supports close clinical monitoring", Child and Adolescent Psychiatry and Mental Health 2 (1): 24, doi:10.1186/1753-2000-2-24, PMC 2566553, PMID 18793403

[6] Wang, M; Ramos, BP (2007), "Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex", Cell 129 (2): 397–410, doi:10.1016/j.cell.2007.03.015, PMID 17448997

[7] Jäkälä P, Riekkinen M, Sirviö J, Koivisto E, Kejonen K, Vanhanen M, Riekkinen P Jr. Guanfacine, but not clonidine, improves planning and working memory performance in humans. Neuropsychopharmacology. 20:460-70, 1999.

[8] Müller, U; Clark, L; Lam, ML; Moore, RM; Murphy, CL; Richmond, NK; Sandhu, RS; Wilkins, IA et al. (2005), "Lack of effects of guanfacine on executive and memory functions in healthy male volunteers", Psychopharmacology 182 (2): 205–13, doi:10.1007/s00213-005-0078-4, PMID 16078088.

[9] Kaminer, D.; Seedat, S. & Stein, D. (2005), "Post-traumatic stress disorder in children", World Psychiatry 4 (2): 121–125, PMC 1414752, PMID 16633528 .

[10] Kozarlc-Kovaclc, D. (2008), "Psychopharmacotherapy of Posttraumatic Stress Disorder", Croatian Medical Journal 49 (4): 459–475, doi:10.3325/cmj.2008.4.459, PMC 2525822, PMID 18716993 .

[11] Sofuogul, M. & Sewell, A. (2009), "Norepinephrine and Stimulant Addiction", Addiction Biology 14 (2): 119–129, doi:10.1111/j.1369-1600.2008.00138.x, PMC 2657197, PMID 18811678

[12] "Intuniv for ADHD: Efficacy, Side Effects". Health and Life. http://healthlifeandstuff.com/2009/09/intuniv-for-adhd-concerns-efficacy/.

[13] "ADHD Drugs and Side Effects in Children". http://health.ltgovernors.com/mental-health/adhd-drugs-and-side-effects-in-children.html.

[14] Vitiello B (April 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): 459–74, xi, doi:10.1016/j.chc.2007.11.010, PMC 2408826, PMID 18295156.

[Kiechel-15] Kiechel, J. (1980), "Pharmacokinetics and metabolism of guanfacine in man: A review", British Journal of Clinical Pharmacology 10 (Suppl 1): 25S–32S, PMC 1430131, PMID 6994775 .

[16] Kirch, W.; Kohler, H. & Braun, W. (1980), "Elimination of guanfacine in patients with normal and impaired renal function", British Journal of Clinical Pharmacology 10 (Suppl 1): 33S–35S, PMC 1430110, PMID 6994776 .

[17] Ramos, Brian P.; Stark, David; Verduzco, Luis; van Dyck, Christopher H.; Arnsten, Amy F. T. (2006), "α2A-adrenoceptor stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals", Learning & Memory 13 (6): 770–776, doi:10.1101/lm.298006, PMC 1783631, PMID 17101879 .

リンク元	「グアンファシン」「グァンファシン」
関連記事	「hydrochloride」

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案内

guanfacine hydrochloride