Drug/Small Molecule:
lofexidine

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PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

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The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • 2-(1-(2,6-Dichlorophenoxy)ethyl)-4,5-dihydro-1H-imidazole
  • 2-(alpha-(2,6-Dichlorophenoxy)ethyl)2-imidazoline
  • Lofexidina [inn-spanish]
  • Lofexidine hydrochloride
  • Lofexidinum [inn-latin]
  • lofexidine
Trade Names
  • BritLofex
Brand Mixture Names

PharmGKB Accession Id:
PA164744510

Description

Lofexidine is an alpha2-adrenergic receptor agonist. It can be used as a short acting anti-hypertensive, but is mostly used to help relieve symptoms of heroin or opiate withdrawal in opiate dependency. It is approved in the United Kingdom, but is still undergoing clinical trials in the United States.

Source: Drug Bank

Indication

Investigated for use/treatment in addictions and substance abuse.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Lofexidine is an alpha2-adrenergic receptor agonist.

Source: Drug Bank

Pharmacology

Lofexidine is an orally active imidazoline adrenergic alpha-2-receptor agonist; and is believed to have a high affinity for 2A receptor subtypes resulting in less anti-hypertensive activity than clonidine, a non-selective alpha-2-receptor agonist. Hypotension may occur in susceptible subjects, accompanied by a decrease in heart rate. Abrupt discontinuation of lofexidine has been, in some cases, associated with a transient increase in blood pressure to higher than pre-treatment levels. It selectively stimulates receptors in the brain that monitor catecholamine levels in the blood. These receptors close a negative feedback loop that begins with descending sympathetic nerves from the brain that control the production of catecholamines (epinephrine, also known as adrenaline, and norepinephrine) in the adrenal medulla. By fooling the brain into believing that catecholamine levels are higher than they really are, lofexidine causes the brain to reduce its signals to the adrenal medulla, which in turn lowers catecholamine production and blood levels. The result is a lowered heart rate and blood pressure. This central action is responsible for the suppression of opiate withdrawal symptoms.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Lofexidine undergoes extensive metabolism in the liver and excretion is mainly by the kidney.

Source: Drug Bank

Protein Binding

80 to 90%

Source: Drug Bank

Absorption

Lofexidine is extensively absorbed and achieves peak plasma concentration at
3 hours after administration of a single dose. Bioavailability is over 90% following oral administration.

Source: Drug Bank

Half-Life

11 hours

Source: Drug Bank

Toxicity

Lofexidine was tolerated at high dosage in singe dose toxicity studies in animals, the LD 50 being >77 mg/kg. With repeat dosing in mice, rats and dogs symptoms related to the pharmacology of the drug (ataxia, sedation, tremor, unkempt appearance and exhaustion) appeared. Overdosage may cause hypotension, bradycardia and sedation.

Source: Drug Bank

Chemical Properties

Chemical Formula

C11H12Cl2N2O

Source: Drug Bank

Isomeric SMILES

C[C@@H](C1=NCCN1)OC2=C(C=CC=C2Cl)Cl

Source: Drug Bank

CC(OC1=C(Cl)C=CC=C1Cl)C1=NCCN1

Source: Drug Bank

Canonical SMILES

CC(OC1=C(Cl)C=CC=C1Cl)C1=NCCN1

Source: Drug Bank

Average Molecular Weight

259.132

Source: Drug Bank

Monoisotopic Molecular Weight

258.03266843

Source: Drug Bank

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB04948
ChEBI:
51368
PubChem Compound:
30668
PubChem Substance:
14774610
46508453
ChemSpider:
28460
Therapeutic Targets Database:
DAP000064

Clinical Trials

These are trials that mention lofexidine and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.