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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/20 19:47:58」(JST)

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Lofexidine is an alpha2-adrenergic receptor agonist, historically used as a short-acting anti-hypertensive, but more commonly used to alleviate physical symptoms of heroin and opiate withdrawal.

Indication[edit]

In the United Kingdom, the hydrochloride form, lofexidine HCl, has been licensed and sold since 1992 for opiate withdrawal relief in tablet form as BritLofex by Britannia Pharmaceuticals. BritLofex is only available by prescription. Lofexidine is also commonly used in conjunction with the opioid receptor antagonist naltrexone in rapid detoxification cases. When these two drugs are paired, naltrexone is administered to induce an opioid-receptor blockade sending the subject into immediate withdrawal and accelerating the detoxification process, while lofexidine is given to relieve the symptoms associated with the withdrawal including chills, sweating, stomach cramps, muscle pain, and runny nose. Lofexidine inhibits the release of norepinephrine in the central and peripheral nervous system, thereby reducing some of the withdrawal symptoms, but it has no documented effect on drug craving and endogenous opioid levels.^[1]

Use in opioid detoxification[edit]

Lofexidine is not an opioid, whereas methadone is. Some opioid detox programs use methadone in decreasing amounts in their detox protocol, whereas other detox programs use lofexidine. The drugs are completely chemically unrelated, and their physiological effects are completely unrelated, although both are used as part of an opioid detoxification protocol. Whereas lofexidine cannot stop opioid withdrawal and merely eases some symptoms of withdrawal, methadone—being an opioid itself—will completely ameliorate all withdrawal symptoms in a sufficient dose. Indeed, one suggested use for lofexidine is to ease withdrawal symptoms of methadone dependence. While abstaining from opiates and taking lofexidine, effective detoxification can succeed in as little as 3 days^[2] , although the standard duration of detoxification using lofexidine is 10 days.^[3] The LD₅₀ of lofexidine is 77 mg/kg. Lofexidine is not currently available in the United States. Britannia Pharmaceuticals has licensed lofexidine to be sold by US World Meds for sale in North America,^[4] and clinical trials are currently underway to secure approval for sale in the United States by the U.S. Food and Drug Administration (FDA).^[5]

An additional benefit of lofexidine treatment is that it is given as part of an outpatient, or ambulatory regimen, and can be completed without a hospital stay. This reduces costs for both healthcare provider and patient, and keeps specialist hospital beds free for particularly difficult withdrawal cases.

Structural similarities to clonidine[edit]

Structure of Lofexidine and Clonidine

Lofexidine is structurally analogous to clonidine, another alpha2-adrenergic receptor agonist used for treatment of opioid withdrawal symptoms. A comparison of the two structures is shown at right. Both contain an imidazole ring and a 2,6-dichlorinated phenyl ring. The differences in structure are shown in red, while the similarities are in black. In addition to the structural differences, administration of lofexidine in heroin addicts has been shown to be more effective for a longer duration, with fewer withdrawal symptoms than clonidine even after one day.^[2] However, Clonidine is often preferred as it is substantially cheaper than Lofexidine when purchased with a private (non-NHS) prescription. This factor is exacerbated by the considerable number of and quantities of medications prescribed to alleviate the constellation of withdrawal signs and symptoms. Additionally, clonidine has been shown to significantly lower blood pressure. Therefore, although similar to lofexidine, clonidine is most frequently prescribed to treat high-blood pressure.

Other clinical uses[edit]

The possibility of using lofexidine to treat alcohol addiction withdrawal symptoms has been investigated, and has not yet been shown to be an effective treatment.^[6]

Additionally, the possibility of lofexidine to treat ADHD symptoms in children has been investigated.^[7] Although this subject has only a small body of research, when a small dose of lofexidine is given (0.4 mg, 3x daily), ADHD severity significantly decreased. Similar studies have shown reduction of tics in children with the small dosage.^[7]

Adverse side effects[edit]

Drowsiness
Dry mouth
Dry Nose
Hypotension
Dizziness^[8]

References[edit]

^ http://www.drugs-forum.com/forum/showwiki.php?title=Lofexidine
^ ^a ^b G. Gerra, et al., Lofexidine versus clonidine in rapid opiate detoxification, Journal of Substance Abuse TreatmentVolume 21, Issue 1, , July 2001, Pages 11-17.
^ J. Bearn, M. Gossop, J. Strang, Drug Alcohol Depend. 43, 87 (1996)
^ Britannia Pharmaceuticals Limited
^ US WorldMeds | +1 502 893 3235
^ Keaney F, Strang J, Gossop M, Marshall EJ, Farrell M, Welch S, Hahn B, Gonzalez A. A double-blind randomized placebo-controlled trial of lofexidine in alcohol withdrawal: lofexidine is not a useful adjunct to chlordiazepoxide. Alcohol Alcohol (2001) 36:426–30.
^ ^a ^b Niederhofer H, Staffen W, Mair A: A placebo-controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. J Psychopharmacol 2003, 17:113-119.
^ http://www.lofexidine.co.uk/leaflets/bfl-pil-v4_07-2006.pdf

External links[edit]

BritLofex Official Website

UpToDate Contents

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1. オピオイド中毒治療中の医師監督下の離脱 medically supervised opioid withdrawal during treatment for addiction
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3. 緊急時のオピオイド離脱 opioid withdrawal in the emergency setting
4. Complementary and alternative treatments for anxiety symptoms and disorders: Physical, cognitive, and spiritual interventions
5. クロニジンおよびイミダゾリンによる中毒 clonidine and related imidazoline poisoning

English Journal

Is it prime time for alpha2-adrenocepter agonists in the treatment of withdrawal syndromes?

Albertson TE1, Chenoweth J, Ford J, Owen K, Sutter ME.
Journal of medical toxicology : official journal of the American College of Medical Toxicology.J Med Toxicol.2014 Dec;10(4):369-81. doi: 10.1007/s13181-014-0430-3.
The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search using alpha2-adrenoreceptor agonist (A2AA), specific A2AA agents, withdrawal syndrome and nicotine, and alcohol and opioid withdrawa
PMID 25238670

The preclinical discovery of lofexidine for the treatment of opiate addiction.

Vartak AP1.
Expert opinion on drug discovery.Expert Opin Drug Discov.2014 Nov;9(11):1371-7. doi: 10.1517/17460441.2014.962995. Epub 2014 Sep 26.
INTRODUCTION: Lofexidine is one therapeutic option used for treating the onslaught of sympathetic outflow that typically commences upon induction of opiate withdrawal. It was approved for opiate detoxification in the UK, most of EU, and a select few countries worldwide during the 1980s and the 90s.
PMID 25260380

Dual effects of α2 -adrenoceptors in modulating myogenic tone in sheep isolated internal anal sphincter.

Rayment SJ1, Simpson JA, Eames T, Acheson AG, Dashwood MR, Henry Y, Gruss H, Scholefield JH, Wilson VG.
Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.Neurogastroenterol Motil.2014 Aug;26(8):1095-103. doi: 10.1111/nmo.12363. Epub 2014 Jun 6.
BACKGROUND: The role of α-adrenoceptors in promoting continence through modulation of sphincter tone has focused primarily on the effects of α1 -adrenoceptors. We have used three clinically available agents, which are selective for α2 -adrenoceptors, to investigate their role in contractile and n
PMID 24906134

Japanese Journal

Lofexidine for opiate detoxification : Review of recent randamised and open controlled trials

STRANG J.
Am J Addict 8, 337-348, 1999
NAID 30016952542

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「ロフェキシジン」

Lofexidine
Systematic (IUPAC) name
	(RS)-2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole
Clinical data
AHFS/Drugs.com	International Drug Names
Legal status	Prescription Only (S4) (AU) POM (UK)
Routes	Oral
Pharmacokinetic data
Bioavailability	>90%
Protein binding	80–90%
Metabolism	Hepatic glucuronidation
Half-life	11 hours
Excretion	Renal
Identifiers
CAS number	31036-80-3
ATC code	N07BC04
PubChem	CID 30668
DrugBank	DB04948
ChemSpider	28460
UNII	UI82K0T627
KEGG	D08141
ChEBI	CHEBI:51368
ChEMBL	CHEMBL17860
Chemical data
Formula	C11H12Cl2N2O
Mol. mass	259.131 g/mol
	SMILES Clc2c(OC(C/1=N/CCN\1)C)c(Cl)ccc2;
	InChI InChI=1S/C11H12Cl2N2O/c1-7(11-14-5-6-15-11)16-10-8(12)3-2-4-9(10)13/h2-4,7H,5-6H2,1H3,(H,14,15) ; Key:KSMAGQUYOIHWFS-UHFFFAOYSA-N ;
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英: lofexidine

-lofexidine

[1] ttp://www.drugs-forum.com/forum/showwiki.php?title=Lofexidine

[gerra-2] G. Gerra, et al., Lofexidine versus clonidine in rapid opiate detoxification, Journal of Substance Abuse TreatmentVolume 21, Issue 1, , July 2001, Pages 11-17.

[3] J. Bearn, M. Gossop, J. Strang, Drug Alcohol Depend. 43, 87 (1996)

[4] Britannia Pharmaceuticals Limited

[5] US WorldMeds | +1 502 893 3235

[6] Keaney F, Strang J, Gossop M, Marshall EJ, Farrell M, Welch S, Hahn B, Gonzalez A. A double-blind randomized placebo-controlled trial of lofexidine in alcohol withdrawal: lofexidine is not a useful adjunct to chlordiazepoxide. Alcohol Alcohol (2001) 36:426–30.

[nied-7] Niederhofer H, Staffen W, Mair A: A placebo-controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. J Psychopharmacol 2003, 17:113-119.

[8] ttp://www.lofexidine.co.uk/leaflets/bfl-pil-v4_07-2006.pdf

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