General
Preferred name
LORAZEPAM
Synonyms
Lorazepam-13C2-d4 ()
Lorazepam-13C2-d4 (CRM) ()
Ativan ()
Lorazepam Intensol ()
Lorazepam Preservative Free ()
Loraz ()
Abbloraz ()
Temesta ()
Lorazepam civ ()
WY-4036 ()
NSC-289758 ()
Loreev xr ()
P&D ID
PD003117
CAS
846-49-1
2747915-04-2
Tags
natural product
drug
available
Approved by
FDA
First approval
1977
Drug indication
Tranquilizer (minor)
Anxiety disorder
Drug Status
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ABSORPTION
Readily absorbed with an absolute bioavailability of 90% when given orally. When intramuscularly administered a dose of 4 mg, lorazepam is completely and rapidly absorbed and achieves a maximal serum concentration of 48 ng/ml in 15-30 minutes. When administered orally, the time to attained maximum concentration is observed to be of 2 hours.[T385]
PHARMACODYNAMICS
The effect of lorazepam in GABA-A receptors produces an increase in the frequency of opening of the chloride ion channel. However, for its effect to generate, the neurotransmitter is required.[A5415] The anticonvulsant properties of lorazepam are thought to be related to the binding to voltage-dependent sodium channels in which the sustained repetitive firing gets limited by the slow recovery of sodium channels due to the benzodiazepine effect.[A1240] The effect of lorazepam seems to be very compartmental which was observed with a different generation of sleepiness and a dizziness effect.[A173920]
MOA
Lorazepam allosterically binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane.[T385] According to the binding site of lorazepam, we can observe different activities as the binding in the amygdala is known to help mainly in anxiety disorders while the binding in the cerebral cortex helps in seizure disorders.[T385]
ROE
When a single 2 mg oral dose is given to healthy subjects, 88% of the administered dose is recovered in urine and 7% was recovered in feces. From the excreted dose in urine, the major form is the glucuronide version that represents 74% while only 0.3% of the dose is recovered as unchanged lorazepam.[T388]
INDICATION
Lorazepam is FDA-approved for the short-term relief of anxiety symptoms related to anxiety disorders and anxiety associated with depressive symptoms such as anxiety-associated insomnia. It is as well used as an anesthesia premedication in adults to relieve anxiety or to produce sedation/amnesia and for the treatment of status epilepticus.[T385] Some off-label indications of lorazepam include rapid tranquilization of an agitated patient, alcohol withdrawal delirium, alcohol withdrawal syndrome, muscle spasms, insomnia, panic disorder, delirium, chemotherapy-associated anticipatory nausea and vomiting, and psychogenic catatonia.[T385]
TOXICITY
The LD50 observed by oral administration in a mouse is of 1850 mg/kg. When an overdose administration is registered, signs of CNS and respiratory depression are rapidly observed. An overdose stage can result in profound sedation, deep respiratory depression, coma, and death.[T385] When overdose is observed, it is recommended to administer emergency symptomatic medical support with attention to produce an increase in lorazepam elimination.[T388] There is no evidence of carcinogenicity nor mutagenicity. At doses higher than 40 mg/kg there is evidence of fetal resorption and increase in fetal loss.[FDA label]
HALF-LIFE
When administered parentally, the registered half-life of lorazepam is of 14 hours.[T385]
METABOLISM
Lorazepam is hepatically metabolized by CYP450 isoenzymes and extensively conjugated to the 3-0-phenolic glucuronide.[T385] This is an inactive metabolite and is eliminated mainly by the kidneys.
PHARMACODYNAMICS
The effect of lorazepam in GABA-A receptors produces an increase in the frequency of opening of the chloride ion channel. However, for its effect to generate, the neurotransmitter is required.[A5415] The anticonvulsant properties of lorazepam are thought to be related to the binding to voltage-dependent sodium channels in which the sustained repetitive firing gets limited by the slow recovery of sodium channels due to the benzodiazepine effect.[A1240]; ; The effect of lorazepam seems to be very compartmental which was observed with a different generation of sleepiness and a dizziness effect.[A173920]
MOA
Lorazepam allosterically binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane.[T385]; ; According to the binding site of lorazepam, we can observe different activities as the binding in the amygdala is known to help mainly in anxiety disorders while the binding in the cerebral cortex helps in seizure disorders.[T385]
INDICATION
Lorazepam is FDA-approved for the short-term relief of anxiety symptoms related to anxiety disorders and anxiety associated with depressive symptoms such as anxiety-associated insomnia. It is as well used as an anesthesia premedication in adults to relieve anxiety or to produce sedation/amnesia and for the treatment of status epilepticus.[T385]; ; Some off-label indications of lorazepam include rapid tranquilization of an agitated patient, alcohol withdrawal delirium, alcohol withdrawal syndrome, muscle spasms, insomnia, panic disorder, delirium, chemotherapy-associated anticipatory nausea and vomiting, and psychogenic catatonia.[T385]
DESCRIPTION
Lorazepam is used for the short-term management of severe anxiety. where it is thought to have a high affinity for GABA receptors. In March of 2016 it has also been reported as a GPR68 surrogate allosteric ligand .
(GtoPdb)
TOXICITY
The LD50 observed by oral administration in a mouse is of 1850 mg/kg.[L6403] When an overdose administration is registered, signs of CNS and respiratory depression are rapidly observed. An overdose stage can result in profound sedation, deep respiratory depression, coma, and death.[T385] When overdose is observed, it is recommended to administer emergency symptomatic medical support with attention to produce an increase in lorazepam elimination.[T388]; ; There is no evidence of carcinogenicity nor mutagenicity. At doses higher than 40 mg/kg there is evidence of fetal resorption and increase in fetal loss.[FDA label]
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
19
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Guide to Pharmacology
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
NPC Screening Collection
ReFrame library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
43
Molecular Weight
320.01
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
2
Rotatable Bonds
1
Ring Count
3
Aromatic Ring Count
2
cLogP
3.1
TPSA
61.69
Fraction CSP3
0.07
Chiral centers
1.0
Largest ring
7.0
QED
0.85
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Therapeutic Class
Antianxiety Agents
Source data
