LEVLOFEXIDINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H12Cl2N2O
Molecular Weight	259.132
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](OC1=C(Cl)C=CC=C1Cl)C2=NCCN2

InChI

InChIKey=KSMAGQUYOIHWFS-SSDOTTSWSA-N

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)/t7-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C11H12Cl2N2O
Molecular Weight	259.132
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2988468
Curator's Comment: description was created based on several sources, including https://pharm.reviews/images/statyi/british-national-formulary-2015.pdf | https://www.ncbi.nlm.nih.gov/pubmed/2879913 | https://www.drugbank.ca/drugs/DB04948

Levlofexidine is R-enantiomer of a α2A adrenergic receptor agonist Lofexidine. Levlofexidine (as a component of Lofexidine) 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. Lofexidine is approved in the United Kingdom but is still undergoing clinical trials in the United States. Levlofexidine showed an approximately 9-fold higher affinity than Dexlofexidine for the alpha 2-adrenoceptor-like binding sites in rat brain membranes identified by [3H]-clonidine and was 4 times more potent at displacing [3H]-prazosin from alpha 1-adrenoceptors. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor alpha-2 113 Target ID: CHEMBL2095158 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2988468	Agonist 2678
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2988468	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Opioid withdrawal 4 Sources: https://clinicaltrials.gov/ct2/show/NCT02363998	Primary	Approved 8429	Lofexidine Approved Use Unknown
Marijuana dependence 5 Sources: https://clinicaltrials.gov/ct2/show/NCT00373503	Primary	Phase II 1132	Lofexidine Approved Use Unknown
Cocaine-related disorders 19 Sources: https://clinicaltrials.gov/ct2/show/NCT01148992	Primary	Phase I 428	Lofexidine Approved Use Unknown

PubMed

Title	Date	PubMed
Interference of enantiomers of lofexidine with alpha-adrenoceptors.	1985 Jan	2988468

Patents

Sample Use Guides

In Vivo Use Guide

Initially 800 micrograms lofexidine (400 mkg Levlofexidine+400mkg Dexlofexidine) daily in divided doses, increased in steps of 400–800 micrograms daily (max. per dose 800 micrograms) as required for 7–10 days if no opioid use (but longer may be required); maximum 2.4 mg per day

Route of Administration: Oral

In Vitro Use Guide

Rats were decapitated, and the brains, without cerebella, were rapidly removed and stored at -20 C until use. One frozen brain (1.5 g) was homogenized in 20 vol (w/v) of 0.05 mol/L Tris.HC1 buffer (pH 7.7 at 25 "C) by using a glass homogenizer with a Teflon pestle and centrifuged twice at 48000g for 10 min at 4 C. The supernatant was discarded and the resulting pellet was resuspended in 100 mL of ice-cold buffer. In the standard binding assay 1-mL aliquots of the crude membrane homogenate were incubated together with 20 pL of [3H]clonidine (final concentration 2.5 nmol/L) and 50 WL of increasing concentrations of the Levlofexidine at 25 C for 45 min. The incubation was terminated by filtration with Whatman GF/B glass fiber filters.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:10:51 GMT 2023` Edited by `admin` on `Fri Dec 15 16:10:51 GMT 2023`
Record UNII	5SPW497X0Z
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVLOFEXIDINE

Official Name

English

levlofexidine [INN]

Common Name

English

LOFEXIDINE, (R)-

Common Name

English

(-)-(R)-2-(1-(2,6-DICHLOROPHENOXY)ETHYL)-2-IMIDAZOLINE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29709