U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C15H10Cl2N2O2
Molecular Weight 321.1585
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LORAZEPAM

SMILES

c1ccc(c(c1)C2=NC(C(=Nc3ccc(cc32)Cl)O)O)Cl

InChI

InChIKey=DIWRORZWFLOCLC-UHFFFAOYSA-N
InChI=1S/C15H10Cl2N2O2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21H,(H,18,20)

HIDE SMILES / InChI
Lorazepam (brand name Ativan) is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. Lorazepam binds to an allosteric site on GABA-A receptors, which are pentameric ionotropic receptors in the CNS. Binding potentiates the effects of the inhibitory neurotransmitter GABA, which upon binding opens the chloride channel in the receptor, allowing chloride influx and causing hyperpolarization of the neuron. Studies in healthy volunteers show that in single high doses Ativan (lorazepam) has a tranquilizing action on the central nervous system with no appreciable effect on the respiratory or cardiovascular systems. Ativan (lorazepam) is readily absorbed with an absolute bioavailability of 90 percent. The mean half-life of unconjugated lorazepam in human plasma is about 12 hours and for its major metabolite, lorazepam glucuronide, about 18 hours. At clinically relevant concentrations, lorazepam is approximately 85% bound to plasma proteins. Lorazepam is rapidly conjugated at its 3-hydroxy group into lorazepam glucuronide which is then excreted in the urine. Lorazepam glucuronide has no demonstrable CNS activity in animal. Most adverse reactions to benzodiazepines, including CNS effects and respiratory depression, are dose dependent, with more severe effects occurring with high doses. Paradoxical reactions, including anxiety, excitation, agitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, and hallucinations may occur. Small decreases in blood pressure and hypotension may occur but are usually not clinically significant, probably being related to the relief of anxiety produced by lorazepam.

Originator

Curator's Comment:: # Wyeth Pharmaceuticals in 1971

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ATIVAN

Approved Use

Lorazepam is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The effectiveness of lorazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Launch Date

2.44425605E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
20 ng/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LORAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
563.1 ng × h/mL
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LORAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.3 h
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
LORAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
12 h
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LORAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
15%
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LORAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes (pharmacogenomic study)
Comment: The mean systemic clearance of lorazepam decreased by 20% in the inhibited state and increased by 140% in the induced state; UGT2B15*2 polymorphism is a major determinant of interindividual variability with respect to the pharmacokinetics and pharmacodynamics of lorazepam
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Efficacy and withdrawal of clobazam, lorazepam and buspirone in the treatment of anxiety disorders].
1996 Nov-Dec
Butorphanol agonist effects and acute physical dependence in opioid abusers: comparison with morphine.
1998 Dec 1
Acute abstinence syndrome following abrupt cessation of long-term use of tramadol (Ultram): a case study.
2000
Report of severe neurotoxicity with cyclophosphamide.
2000 Nov-Dec
Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective.
2001
Clinical pharmacokinetics of mizolastine.
2001
Biphasic positive airway pressure ventilation (PeV+) in children.
2001
Clotiapine for acute psychotic illnesses.
2001
Role of central histaminergic system in lorazepam withdrawal syndrome in rats.
2001 Apr
Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function assessed by PET at rest and during attentive tasks.
2001 Apr
Neuroleptic malignant syndrome precipitated by promethazine and lorazepam.
2001 Apr
Abuse of topical analgesic.
2001 Apr
Neuroleptic malignant syndrome after addition of haloperidol to atypical antipsychotic.
2001 Apr
Bacterial meningitis in children: critical care needs.
2001 Aug
Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome.
2001 Aug
A double-blind, randomized comparison of i.v. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model.
2001 Aug
Pharmacokinetic-pharmacodynamic modeling and ICU sedation: unexplored territories.
2001 Aug
Maternal exposure to lorazepam and anal atresia in newborns: results from a hypothesis-generating study of benzodiazepines and malformations.
2001 Aug
Haloperidol blood levels in acute mania with psychosis.
2001 Aug
Clinical research on out-of-hospital emergency care.
2001 Aug 30
A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.
2001 Aug 30
Triazolam discrimination in squirrel monkeys distinguishes high-efficacy agonists from other benzodiazepines and non-benzodiazepine drugs.
2001 Feb
Cardiac arrest after fast intravenous infusion of phenytoin mistaken for fosphenytoin.
2001 Feb
Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam.
2001 Feb
Successful management of prolonged gamma-hydroxybutyrate and alcohol withdrawal.
2001 Feb
Sensitive gas chromatographic--mass spectrometric screening of acetylated benzodiazepines.
2001 Feb 23
Diagnosing and managing delirium in the elderly.
2001 Jan
[Instead of benzodiazepines. An antidepressant as sleep aid].
2001 Jan 18
Comparison of ondansetron-dexamethasone-lorazepam versus metoclopramide-dexamethasone-lorazepam in the control of cisplatin induced emesis.
2001 Jul
Successful management of claustrophobia and depression during allogeneic SCT.
2001 Jul
Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma.
2001 Jul
A case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol.
2001 Jul
Comparison of monomeric and polymeric amino acid based surfactants for chiral separations.
2001 Jul 13
[Benzodiazepine consumption: survey of community pharmacies in Aquitaine].
2001 Jul-Aug
Sudden cardiac death with clozapine and sertraline combination.
2001 Jul-Aug
A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].
2001 Jun
The prehospital treatment of status epilepticus (PHTSE) study: design and methodology.
2001 Jun
Modulation of practice-dependent plasticity in human motor cortex.
2001 Jun
Preoperative anxiolysis and postoperative recovery in women undergoing abdominal hysterectomy.
2001 Mar
ECT for prolonged catatonia.
2001 Mar
Discontinuing antidepressants and benzodiazepines upon becoming pregnant. Beware of the risks of abrupt discontinuation.
2001 Mar
Use of ultrasound to prepare lipid emulsions of lorazepam for intravenous injection.
2001 Mar 23
Benzodiazepines and hip fractures in elderly people: case-control study.
2001 Mar 24
Mechanisms influencing stimulus-response properties of the human corticospinal system.
2001 May
Treatment of insomnia in hospitalized patients.
2001 Nov
Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration.
2001 Nov
Sedation in critically ill patients: a review.
2001 Oct
Medication administration errors in adult patients in the ICU.
2001 Oct
De novo absence status of late onset following withdrawal of lorazepam: a case report.
2001 Sep
Pharmacological modulation of behavioral and neuronal correlates of repetition priming.
2001 Sep 1

Sample Use Guides

For optimal results, dose, frequency of administration, and duration of therapy should be individualized according to patient response. To facilitate this, 0.5 mg, 1 mg, and 2 mg tablets are available. The usual range is 2 to 6 mg/day given in divided doses, the largest dose being taken before bedtime, but the daily dosage may vary from 1 to 10 mg/day. For anxiety, most patients require an initial dose of 2 to 3 mg/day given b.i.d. or t.i.d. For insomnia due to anxiety or transient situational stress, a single daily dose of 2 to 4 mg may be given, usually at bedtime. For elderly or debilitated patients, an initial dosage of 1 to 2 mg/day in divided doses is recommended, to be adjusted as needed and tolerated.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: Various ligands for the peripheral benzodiazepine receptors (PBR) displaced [3H]Ro5-4864 binding with the following rank order of potencies: PK11195 = Ro5-4864 > FGIN-1-27 > triazolam = diazepam > beta-pro-pyl-beta-carboline-3-carboxylate = clonazepam > lorazepam = flurazepam >> chlordiazepoxide = clorazepate
Unknown
Name Type Language
LORAZEPAM
EP   INN   MART.   MI   ORANGE BOOK   USAN   USP   VANDF   WHO-DD  
USAN   INN  
Official Name English
LORAZEPAM [WHO-DD]
Common Name English
LORAZEPAM [MI]
Common Name English
LORAZEPAM CIV
USP-RS  
Common Name English
ATIVAN
Brand Name English
LORAZEPAM CIV [USP-RS]
Common Name English
LORAZEPAM [MART.]
Common Name English
LORAZEPAM [JAN]
Common Name English
LORAZEPAM [VANDF]
Common Name English
LORAZEPAM [USAN]
Common Name English
(+/-)-7-CHLORO-5-(O-CHLOROPHENYL)-1,3-DIHYDRO-3-HYDROXY-2H-1,4-BENZODIAZEPIN-2-ONE
Common Name English
LORAZEPAM [USP MONOGRAPH]
Common Name English
2H-1,4-BENZODIAZEPIN-2-ONE, 7-CHLORO-5-(2-CHLOROPHENYL)-1,3-DIHYDRO-3-HYDROXY-, (+/-)-
Systematic Name English
LORAZEPAM [ORANGE BOOK]
Common Name English
LORAZEPAM [EP MONOGRAPH]
Common Name English
LORAZEPAM [EP]
Common Name English
LORAZ
Brand Name English
WY-4036
Code English
LORAZEPAM [INN]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175694
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
DEA NO. 2885
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
WHO-ATC N05BA06
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 05
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
NCI_THESAURUS C1012
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
WHO-VATC QN05BA06
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
WHO-VATC QN05BA56
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
LIVERTOX 571
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
NDF-RT N0000007542
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
NCI_THESAURUS C267
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
WHO-ATC N05BA56
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C619
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
ECHA (EC/EINECS)
212-687-6
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
ChEMBL
CHEMBL580
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
RXCUI
6470
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY RxNorm
MESH
D008140
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
DRUG BANK
DB00186
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
INN
2809
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
PUBCHEM
3958
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
WIKIPEDIA
LORAZEPAM
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
EPA CompTox
846-49-1
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
DRUG CENTRAL
1606
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
MERCK INDEX
M6906
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY Merck Index
FDA UNII
O26FZP769L
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
IUPHAR
5884
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
LACTMED
Lorazepam
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
CAS
846-49-1
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
EVMPD
SUB08582MIG
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY
USP_CATALOG
1370305
Created by admin on Fri Jun 25 21:05:15 UTC 2021 , Edited by admin on Fri Jun 25 21:05:15 UTC 2021
PRIMARY USP-RS