Lorazepam
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Collated from PsychonautWiki, TripSit, Pharmacology, DrugCentral. Where sources differ (e.g. dosing), Compare shows them side by side.
Also known as Lorazepam, Ativan, Orfidal, LorsilanPW
Fatal overdose may occur when benzodiazepines are combined with other depressants such as opiates, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.[1] It is strongly discouraged to combine these substances, particularly in common to heavy doses.PW
Oral
Route dataPsychonautWiki
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| 0.1 mg | 0.25–0.5 mg | 0.5–1.5 mg | 1.5–2 mg | 2 mg+ |
| Total | 4–8 hours |
|---|
Intramuscular
Route dataTripSit
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| — | 0.25–0.5 mg | 0.5–1 mg | 1–2 mg | —+ |
| Onset | 5–30 minutes |
|---|---|
| Total | 4–8 hours |
| After-effects | 1–12 hours |
🧬 Receptor activityPHDC
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| Unchecked | — | Ki 5.177 nM | CHEMBL | TargetUnchecked Action— AffinityKi 5.177 nM SourceCHEMBL |
| Fatty acid-binding protein, liver | — | Ki 12900 nM | CHEMBL | TargetFatty acid-binding protein, liver Action— AffinityKi 12900 nM SourceCHEMBL |
| GABA-A receptor alpha-1/beta-3/gamma-2 (GABRA1) | Positive allosteric modulator | 8.456 IC50 | DRUGCENTRAL | TargetGABA-A receptor alpha-1/beta-3/gamma-2 (GABRA1) ActionPositive allosteric modulator Affinity8.456 IC50 SourceDRUGCENTRAL |
| Fatty acid-binding protein, liver (Fabp1) | — | 4.89 Ki | DRUGCENTRAL | TargetFatty acid-binding protein, liver (Fabp1) Action— Affinity4.89 Ki SourceDRUGCENTRAL |
Mechanism of actionPH
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. 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.
PharmacodynamicsPH
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. 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. The effect of lorazepam seems to be very compartmental which was observed with a different generation of sleepiness and a dizziness effect.
Pharmacokinetics
Half-lifePH
When administered parentally, the registered half-life of lorazepam is of 14 hours. Following the administration of 1 mg of lorazepam in healthy adult male volunteers and using a multi-doses equation based on a one-compartment model, the average elimination half-life of lorazepam was estimated to be 11 hours and 8 hours for sublingual and oral doses respectively. The absorption half-life was calculated to be 55 minutes for oral doses and 15 minutes for sublingual doses.
AbsorptionPH
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.
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.
The reported volume of distribution of lorazepam is 1.3 L/kg. It is important to mention that due to the lipophilicity of lorazepam, it does not redistribute as fast in the brain.
_In vivo_ studies with lorazepam have shown a clearance rate of 5.8 ml.min/kg.
MetabolismPH
Lorazepam is hepatically metabolized by CYP450 isoenzymes and extensively conjugated to the 3-0-phenolic glucuronide. This is an inactive metabolite and is eliminated mainly by the kidneys.
Lorazepam has known human metabolites that include Lorazepam glucuronide.
Lorazepam is hepatically metabolized and is extensively conjugated to the 3-0-phenolic glucuronide. This is an inactive metabolite and is eliminated mainly by the kidneys.
Route of Elimination: When a single 2 mg oral dose is give to healthy subjects, 88±4% of the administered dose was recovered in urine and 7±2% was recovered in feces. The percent of administered dose recovered in urine as lorazepam glucuronide was 74±4%. Only 0.3% of the dose was recovered as unchanged lorazepam, and the remainder of the radioactivity represented minor metabolites.
Half Life: Parenteral administration = 14±5 hours;
Oral administration = 2 hours.
Protein bindingPH
Reports indicate that 85% of lorazepam administered dose is protein bound.
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External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.