← hubDrugs

Clorazepate

Discover related
Class
Dose
Duration

3 sources

← All substances
🔗 MergedCompareTripSitPharmacologyDrugCentral

Collated from TripSit, Pharmacology, DrugCentral. Where sources differ (e.g. dosing), Compare shows them side by side.

Sections
DepressantBenzodiazepineHabit-formingTS

Also known as tranxene, novo-clopate, tranzeneTS

Is a prodrug for Desmethyldiazepam which is responsible for most of the therapeutic effects. Has a long half life, with the addition of Desmethyldiazepam as the main metabolite, which makes it much longer.TS

Oral

Route dataTripSit

Dose
WeakerStronger
ThresholdLightCommonStrongHeavy
—5–10 mg10–20 mg20–40 mg—+
040 mg
LightCommonStrongHeavy
Duration
ShorterLonger
Onset20–80 minutes
Total8–12 hours
After-effects1–8 hours
OnsetCome-upPeakOffset

🧬 Receptor activityDC

TargetActionAffinitySource
GABA-A receptor alpha-1/beta-2/gamma-2 (GABRA1)Positive allosteric modulator7.47 EC50DRUGCENTRAL
GABA-A receptor alpha-2/beta-3/gamma-2 (GABRG2)Positive allosteric modulator—DRUGCENTRAL
GABA-A receptor alpha-3/beta-3/gamma-2 (GABRG2)Positive allosteric modulator—DRUGCENTRAL
GABA-A receptor alpha-5/beta-3/gamma-2 (GABRG2)Positive allosteric modulator—DRUGCENTRAL
‹ PrevPage 1 / 11–4 of 4Next ›

Mechanism of actionPH

Clorazepate is a benzodiazepine with depressant effects on the central nervous system. Benzodiazepines are able to enhance the binding of gamma-aminobutyric acid (GABA) to the GABA type A (GABA-A) receptor by binding to a region in the extracellular domain found at the interface between the alpha (α) and gamma (γ) subunits of the GABA-A receptor. The interaction of GABA and the GABA-A receptor promotes channel opening, leading to an increased chloride influx. Consequently, the use of benzodiazepines, such as clorazepate, leads to neuronal hyperpolarization.
The effects of benzodiazepines on the waking EEG resemble those of other sedative-hypnotic drugs. Alpha activity is decreased, and there is an increase in low-voltage fast activity, especially beta activity. /Benzodiazepines/
Acticonvulsant actions of the benzodiazepines, as well as other effects that occur at nonsedating doses, result in large part from their ability to enhance GABA-induced increases in the conductance of chloride. /Benzodiazepines/
Benzodiazepines appear to produce their sedative, hypnotic, anxiolytic, and anticonvulsant actions by binding to specific pharmacologic receptors in the central nervous system. Benzodiazepine receptors are most concentrated in the cerebral cortex but are also found in the cerebellum, amygdala, hippocampus, hypothalamus, and spinal cord. Receptors have also been identified outside CNS, although peripheral receptors do not appear to have significant physiologic effects. The molecular receptor for the benzodiazepine molecule is a glycoprotein located on the lipid membranes of both neural and glial cells. It is speculated that there are at least two classes of benzodiazepine receptor believed to mediate different specific effects. Type I receptors predominate in the cerebelar cortex, and both type I and type II receptors are found in the cerebral cortex and hippocampus. Type I rceptors are postulated to mediate anxiolytic effects, and type II receptors mediate the sedative and other actions of benzodiazepines. No endogenous ligand or neurotransmitter for these receptors has been identified. /Benzodiazepines/

PharmacodynamicsPH

Pharmacologically, clorazepate has the characteristics of benzodiazepines. Studies in healthy men have shown that clorazepate has depressant effects on the central nervous system. Since orally administered clorazepate dipotassium is rapidly decarboxylated to form nordiazepam, there is essentially no circulating parent drug. The use of benzodiazepines, including clorazepate, exposes users to abuse, misuse, and addiction risks, which can lead to overdose and death. Patients treated with clorazepate may also develop suicidal behavior and ideation, and the use of clorazepate may cause interference with psychomotor performance. The concomitant use of clorazepate with opioids may result in profound sedation, respiratory depression, coma, and death.

Pharmacokinetics

Half-lifePH

The serum half-life of clorazepate is approximately 2 days. Nordiazepam, the primary metabolite, quickly appears in the blood and is eliminated from the plasma with an apparent half-life of about 40 to 50 hours.
PLASMA HALF-LIFE ... 53 HR ... .
PRIMARY METABOLITE, NORDIAZEPAM, ... PLASMA HALF-LIFE IS ABOUT 24 HR.
N-DIMETHYLDIAZEPAM, METABOLITE OF CHLORAZEPATE: MEAN HALF-LIFE 62 HR.
CLORAZEPATE ADMIN IM TO PREGNANT & NONPREGNANT WOMEN. ELIMINATION HALF-LIFE WERE 1.3 HR IN PREGNANT WOMEN & 2.0 HR IN NONPREGNANT WOMEN. ITS METABOLITE, NORDIAZEPAM, REACHED PEAK CONCN WITHIN 12 HR. HALF-LIFE OF ELIMINATION FOR METABOLITE WAS 180 IN PREGNANT & 60 HR IN NONPREGNANT WOMEN.
Elimination half-lives for metabolites: desmethyldiazepam (30-200 hr) and oxazepam (3-21 hr)

AbsorptionPH

Clorazepate is a prodrug for nordiazepam, and this conversion occurs almost entirely before entering systemic circulation. Therefore, the pharmacokinetic parameters of clorazepate are based on nordiazepam concentrations. In healthy volunteers given a 20 mg oral dose of clorazepate, nordiazepam had a peak plasma level of 356 ng/mL, which was reached approximately 0.9 h after the administration of clorazepate. The plasma levels of nordiazepam increase proportionally with the clorazepate dose and show moderate accumulation with repeated administration. The oral bioavailability of clorazepate is 91%.
Clorazepate is mainly excreted through urine and feces. In two volunteers given 15 mg of [14C]-clorazepate, 62-67% of the radioactivity was excreted in the urine and 15-19% was eliminated in the feces within 10 days. On day 10, both subjects were still excreting about 1% of the [14C]-dose in the urine.
Following a single 20 mg intravenous dose, the volume of distribution of nordiazepam (active metabolite of clorazepate) was 1.24 L/kg.
Following a single 20 mg intravenous dose, nordiazepam (the active metabolite of clorazepate) had a total clearance of 0.24 mL/min/kg.
PRIMARY METABOLITE, NORDIAZEPAM, REACHES PEAK LEVELS IN PLASMA IN 1 HR; PLASMA HALF-LIFE IS ABOUT 24 HR.
PLASMA HALF-LIFE ELIMINATION COEF, CONCN, & APPARENT VOL OF DISTRIBUTION CALCULATED & MEAN VALUES WERE 53 HR, 0.0147 HR-1, 884 NG/ML, & 1.13 L/KG.

MetabolismPH

Clorazepate is metabolized in the liver and excreted mainly through urine. Following oral administration, clorazepate is decarboxylated by the gastric acid of the stomach before absorption. The primary metabolite, nordiazepam, is further metabolized by hydroxylation. The major urinary metabolite is conjugated oxazepam (3-hydroxynordiazepam), and smaller amounts of conjugated p-hydroxynordiazepam and nordiazepam are also found in the urine.
CHLORAZEPATE IS PROBABLY CONVERTED TO N-DIMETHYL DIAZEPAM, WHICH IS THEN OXIDIZED TO OXAZEPAM. /CHLORAZEPATE/
PRIMARY METABOLITE /IS/ NORDIAZEPAM ... .
Following oral administration of clorazepate dipotassium, it appears that most of the drug is rapidly decarboxylated in the GI tract and is absorbed as desmethyldiazepam (nordiazepam). The rate of decarboxylation of clorazepate decreases as gastric pH increases. /Clorazepate dipotassium/
Clorazepate active metabolites in liver are desmethyldiazepam, and oxazepam; active substances in blood include desmethyldiazepam. /From table/
For more Metabolism/Metabolites (Complete) data for CLORAZEPATE (8 total), please visit the HSDB record page.

Protein bindingPH

The protein binding of nordiazepam (active metabolite of clorazepate) in plasma is high (97-98%).

Plan when to take Clorazepate — see where onset, peak and comedown land on the clock

Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.