ID

DB00186|APRD00116||

名称

Lorazepam

描述

Lorazepam is a short-acting and rapidly cleared benzodiazepine used commonly as a sedative and anxiolytic.[A957] It was developed by DJ Richards, presented and marketed initially by Wyeth Pharmaceuticals in the USA in 1977. The first historic FDA label approval is reported in 1985 by the company Mutual Pharm.[L5095]

cas号

846-49-1

唯一标识码

O26FZP769L

状态

solid

组

approved,

指示

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]

药效学

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]

作用机制

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]

毒性

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]

代谢

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.

吸收

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]

半衰期

When administered parentally, the registered half-life of lorazepam is of 14 hours.[T385]

分类

description:This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
direct-parent:1,4-benzodiazepines
kingdom:Organic compounds
superclass:Organoheterocyclic compounds
class:Benzodiazepines
subclass:1,4-benzodiazepines
alternative-parent:Alkanolamines
alternative-parent:Alpha amino acids and derivatives
alternative-parent:Aryl chlorides
alternative-parent:Azacyclic compounds
alternative-parent:Carbonyl compounds
alternative-parent:Chlorobenzenes
alternative-parent:Hydrocarbon derivatives
alternative-parent:Ketimines
alternative-parent:Lactams
alternative-parent:Organic oxides
alternative-parent:Organochlorides
alternative-parent:Organopnictogen compounds
alternative-parent:Propargyl-type 1,3-dipolar organic compounds
alternative-parent:Secondary carboxylic acid amides
substituent:1,4-benzodiazepine
substituent:Alkanolamine
substituent:Alpha-amino acid or derivatives
substituent:Aromatic heteropolycyclic compound
substituent:Aryl chloride
substituent:Aryl halide
substituent:Azacycle
substituent:Benzenoid
substituent:Carbonyl group
substituent:Carboxamide group
substituent:Carboxylic acid derivative
substituent:Chlorobenzene
substituent:Halobenzene
substituent:Hydrocarbon derivative
substituent:Imine
substituent:Ketimine
substituent:Lactam
substituent:Monocyclic benzene moiety
substituent:Organic 1,3-dipolar compound
substituent:Organic nitrogen compound
substituent:Organic oxide
substituent:Organic oxygen compound
substituent:Organochloride
substituent:Organohalogen compound
substituent:Organonitrogen compound
substituent:Organooxygen compound
substituent:Organopnictogen compound
substituent:Propargyl-type 1,3-dipolar organic compound
substituent:Secondary carboxylic acid amide

消除途径

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]

种类

Anti-Anxiety Agents
D014151
Anticonvulsants
D000927
Antiemetics
D000932
Autonomic Agents
D001337
Benzazepines
D001552
Benzodiazepine hypnotics and sedatives

Benzodiazepines and benzodiazepine derivatives
D001569
Benzodiazepinones
D001570
Central Nervous System Agents
D002491
Central Nervous System Depressants
D002492
Cytochrome P-450 CYP3A Substrates

Cytochrome P-450 CYP3A4 Substrates

Cytochrome P-450 CYP3A4 Substrates (strength unknown)

Cytochrome P-450 Substrates

Drugs that are Mainly Renally Excreted

GABA Agents
D018682
GABA Modulators
D018757
Gastrointestinal Agents
D005765
Heterocyclic Compounds, Fused-Ring
D000072471
Hypnotics and Sedatives
D006993
Muscle Relaxants

Muscle Relaxants, Centrally Acting Agents
D009125
Nervous System
D009420
Neurotransmitter Agents
D018377
Peripheral Nervous System Agents
D018373
Psycholeptics

Psychotropic Drugs
D011619
Tranquilizing Agents
D014149

盐类

蛋白质结合

Reports indicate that 85% of lorazepam administered dose is protein bound.[T388]

清除

_In vivo_ studies with lorazepam have shown a clearance rate of 5.8 ml.min/kg.[A173914]

同义词

language:spanish; code:; name;Loracepam
language:english; code:inn/usan; name;Lorazepam
language:english; code:; name;o-Chlorooxazepam
language:english; code:; name;o-Chloroxazepam

国际品牌

AlmazinePsyco RemediesAnxiedinU-LiangIdalpremNovartisLorabenzLorsilanBelupoSomagerolTemestaWyethWypaxWyeth KK

配送量

The reported volume of distribution of lorazepam is 1.3 L/kg.[T388] It is important to mention that due to the lipophilicity of lorazepam, it does not redistribute as fast in the brain.[T391]

产品

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