Chemical: Drug
lorazepam

PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.



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

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

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.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for lorazepam

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs1902023 NC_000004.11:g.69536084A=, NC_000004.11:g.69536084A>C, NC_000004.12:g.68670366A=, NC_000004.12:g.68670366A>C, NM_001076.3:c.253T=, NM_001076.3:c.253T>G, NP_001067.2:p.Tyr85=, NP_001067.2:p.Tyr85Asp, NT_167250.1:g.248671C=, NT_167250.1:g.248671C>A, NT_167250.2:g.246721C=, NT_167250.2:g.246721C>A, rs141137354, rs52823570, rs57851547
A > C
SNP
Y85D
No VIP available No Clinical Annotations available VA
rs7438284 NC_000004.11:g.69964337A>T, NC_000004.12:g.69098619A>T, NM_001074.2:c.801A>T, NP_001065.2:p.Pro267=, XM_005265702.1:c.54A>T, XM_005265702.2:c.54A>T, XM_011532229.1:c.801A>T, XM_011532230.1:c.801A>T, XM_011532231.1:c.54A>T, XP_005265759.1:p.Pro18=, XP_011530531.1:p.Pro267=, XP_011530532.1:p.Pro267=, XP_011530533.1:p.Pro18=, rs58290492
A > T
SNP
P267P
No VIP available CA VA
rs7439366 NC_000004.11:g.69964338T>C, NC_000004.12:g.69098620T>C, NM_001074.2:c.802T>C, NP_001065.2:p.Tyr268His, XM_005265702.1:c.55T>C, XM_005265702.2:c.55T>C, XM_011532229.1:c.802T>C, XM_011532230.1:c.802T>C, XM_011532231.1:c.55T>C, XP_005265759.1:p.Tyr19His, XP_011530531.1:p.Tyr268His, XP_011530532.1:p.Tyr268His, XP_011530533.1:p.Tyr19His, rs34924067, rs57980137
T > C
SNP
Y268H
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • (+/-)-Lorazepam
  • L-Lorazepam Acetate
  • O-Chlorooxazepam
  • O-Chloroxazepam
Trade Names
  • Almazine
  • Alzapam
  • Anxiedin
  • Aplacassee
  • Ativan
  • Bonatranquan
  • Delormetazepam
  • Emotival
  • Idalprem
  • Lorabenz
  • Lorax
  • Loraz
  • Lorazepam Intensol
  • Lorsilan
  • Pro Dorm
  • Psicopax
  • Punktyl
  • Quait
  • Securit
  • Sedatival
  • Sedazin
  • Somagerol
  • Tavor
  • Temesta
  • Wypax
Brand Mixture Names

PharmGKB Accession Id

PA450267

Type(s):

Drug

Description

A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent.

Source: Drug Bank

Pharmacogenetics

Lorazepam is a benzodiazepine derivative with antianxiety and sedative-hypnotic actions. It is used to treat anxiety disorder. Lorazepam acts by binding to the benzodiazepine site on the GABAA receptor to enhance the affinity of channel opening by the agonist GABA , which leads to central nervous system depression [Articles:11689393, 751612, 18384456, 15926867].

Pharmacokinetics:

The metabolism of lorazepam is non-oxidative and no active metabolite is formed. It is metabolized to a pharmacologically inactive metabolite 3-O-glucuronide [Articles:18855614, 6111408]. Genetic polymorphism of in UGT2B15 (UGT2B15*2, [RSID:rs1902023]) has been found to impact the clearance of lorazepam [Article:15961980]. Deatailed lorazepam metabolism is depicted in the Benzodiazepine PK pathway (http://www.pharmgkb.org/do/serve?objId=PA165111375&objCls=Pathway#).

Pharmacodynamics:

Similar to other benzodiazepine (BDZ) derivatives, the primary target of lorazepam is the GABAa receptor, a pentameric protein which forms a chloride selective ion channel, activated by gamma-aminobutyric acid (GABA) [Articles:11689393, 751612, 18384456]. At least 16 different GABAa receptor subunits have been identified, classified into seven subunit families: α, β, γ, δ, ε, θ and &pi: subunits [Article:18651727]. The most common GABAa-BDZ receptor in the brain is thought to be composed of 2 subunits of alpha1; 2 subunits of beta2 and 1 subunit of gamma2 [Articles:11689393, 12171574, 9426470, 15301992] coded for by GABRA1, GABRB2 and GABRG2 respectively. Lorazepam binds to the cleft between subunits alpha1 and gamma2 on the GABAA receptor to induce a conformational change in the receptor [Articles:12171574, 9426470]. This binding pocket is separate from that of the GABA agonist site, which itself is thought to be between the alpha1 and beta2 subunits [Article:9426470]. The general notion of the action of BZDs is that they promote the binding of the major inhibitory neurotransmitter GABA to the GABAa receptors and enhances the affinity of channel opening by GABA. They do not activate GABAa receptors directly but, instead, are positive allosteric modulators of the effects of GABA [Article:12171574] and allow lower concentrations of this neurotransmitter to open the Cl- channels [Article:12171574].

Besides the GABAa receptor, BDZs also bind to the Peripheral Benzodiazepine Receptor (PBR); this receptor consists of several subunits, including the isoquinoline binding protein (TSPO, also referred to as a translocator protein); a voltage-dependent anion channel VDAC (VDAC1); an adenine nucleotide transporter ANT (SLC25A4); a PBR-associated protein 1 PRAX-1 (BZRAP1); and another PBR-associated protein PAP7 (ACBD3) [Articles:17692008, 9504140, 12173979, 19133775, 16822554, 16337685]. Benzodiazepines are thought to bind to the subunit encoded by the gene TSPO [Articles:17692008, 19133775, 16822554, 16337685]. This receptor is expressed in abundance in many peripheral organs and tissues as well as in the central nervous system, in the latter case, in glia cells [Articles:9504140, 12173979]. Studies have shown that the Peripheral Benzodizepine Receptor may play an important role in the human immune system and take part in the pathophysiological processes of several nervous system disorders [Articles:9504140, 12173979].

The detailed mechanism of action of lorazepam and other BDZs is depicted in the Benzodiazepine PD Pathway at:

http://www.pharmgkb.org/search/pathway/benzodiazepine/benzodiazepine-pd.jsp.

Source: PharmGKB

Indication

For the management of anxiety disorders, and for treatment of status epilepticus.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

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 hyperpolerization of the neuron.

Source: Drug Bank

Pharmacology

Lorazepam, a benzodiazepine not transformed to active metabolites, is used to treat anxiety, status epilepticus, and for sedation induction and anterograde amnesia.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Avoid excessive quantities of coffee or tea (Caffeine).|Take with food.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Source: Drug Bank

Protein Binding

85%

Source: Drug Bank

Absorption

Readily absorbed with an absolute bioavailability of 90%.

Source: Drug Bank

Half-Life

12 hours

Source: Drug Bank

Toxicity

Somnolence, confusion, and coma, LD ~50~=3178mg/kg (orally in mice).

Source: Drug Bank

Route of Elimination

Lorazepam is rapidly conjugated at its 3-hydroxy group into lorazepam glucuronide which is then excreted in the urine.

Source: Drug Bank

Chemical Properties

Chemical Formula

C15H10Cl2N2O2

Source: Drug Bank

Isomeric SMILES

c1ccc(c(c1)C2=NC(C(=O)Nc3c2cc(cc3)Cl)O)Cl

Source: OpenEye

Canonical SMILES

OC1N=C(C2=CC=CC=C2Cl)C2=C(NC1=O)C=CC(Cl)=C2

Source: Drug Bank

Average Molecular Weight

321.158

Source: Drug Bank

Monoisotopic Molecular Weight

320.011932988

Source: Drug Bank

SMILES

OC1N=C(C2=CC=CC=C2Cl)C2=C(NC1=O)C=CC(Cl)=C2

Source: Drug Bank

InChI String

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)

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Benzodiazepine Pathway, Pharmacokinetics
    Diagrammatic representation of the metabolism of different benzodiazepine drugs by candidate genes.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
GABRA1 (source: Drug Bank )
GABRA2 (source: Drug Bank )
GABRA3 (source: Drug Bank )
GABRA4 (source: Drug Bank )
GABRA5 (source: Drug Bank )
GABRA6 (source: Drug Bank )
GABRB1 (source: Drug Bank )
GABRB2 (source: Drug Bank )
GABRB3 (source: Drug Bank )
GABRD (source: Drug Bank )
GABRE (source: Drug Bank )
GABRG1 (source: Drug Bank )
GABRG2 (source: Drug Bank )
GABRG3 (source: Drug Bank )
GABRP (source: Drug Bank )
GABRQ (source: Drug Bank )
GABRR1 (source: Drug Bank )
GABRR2 (source: Drug Bank )
GABRR3 (source: Drug Bank )
TSPO (source: Drug Bank )

Drug Interactions

Interaction Description
clozapine - lorazepam Increased risk of toxicity (source: Drug Bank )
clozapine - lorazepam Increased risk of toxicity (source: Drug Bank )
lorazepam - clozapine Increased risk of toxicity (source: Drug Bank )
lorazepam - clozapine Increased risk of toxicity (source: Drug Bank )
lorazepam - mephenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank )
lorazepam - phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank )
phenytoin - lorazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank )
phenytoin - lorazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank )
triprolidine - lorazepam The CNS depressants, Triprolidine and Lorazepam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank )
triprolidine - lorazepam The CNS depressants, Triprolidine and Lorazepam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank )
valproic acid - lorazepam Valproic acid may increase the serum concentration of Lorazepam by reducing Lorazepam metabolism. The Lorazepam dose should be reduced by 50% during concomitant therapy. Monitor for increased Lorazepam effects and toxicity. (source: Drug Bank )

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to lorazepam: 10

No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Evidence for oxazepam as an in vivo probe of UGT2B15: oxazepam clearance is reduced by UGT2B15 D85Y polymorphism but unaffected by UGT2B17 deletion. British journal of clinical pharmacology. 2009. He Xi, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clinical pharmacology and therapeutics. 2008. Chung J-Y, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers. Clinical pharmacology and therapeutics. 2005. Chung Jae-Yong, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. The Journal of pharmacology and experimental therapeutics. 2004. Court Michael H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The benzodiazepine site of the GABAA receptor: an old target with new potential?. Sleep medicine. 2004. Bateson Alan N. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Mapping of the benzodiazepine recognition site on GABA(A) receptors. Current topics in medicinal chemistry. 2002. Sigel Erwin. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Med-psych drug-drug interactions update. Psychosomatics. 2002. Armstrong Scott C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
New insights into the role of the GABA(A)-benzodiazepine receptor in psychiatric disorder. The British journal of psychiatry : the journal of mental science. 2001. Nutt D J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Inhibitory effect of azole antifungal agents on the glucuronidation of lorazepam using rabbit liver microsomes in vitro. Biological & pharmaceutical bulletin. 2000. Sawamura R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The benzodiazepine binding site of GABAA receptors. Trends in pharmacological sciences. 1997. Sigel E, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0054-3532-44
DrugBank:
DB00186
KEGG Drug:
D00365
PubChem Compound:
3958
PubChem Substance:
156663
46508468
Drugs Product Database (DPD):
2243278
ChemSpider:
3821
Therapeutic Targets Database:
DAP000237
FDA Drug Label at DailyMed:
5ff82103-cc57-4af9-9362-82a7c686271d

Clinical Trials

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

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, PubChem.