CLORAZEPATE MONOPOTASSIUM

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H10ClN2O3.K
Molecular Weight	352.814
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[K+].[O-]C(=O)C1N=C(C2=CC=CC=C2)C3=C(NC1=O)C=CC(Cl)=C3

InChI

InChIKey=ULEUKTXFAJZAAV-UHFFFAOYSA-M

InChI=1S/C16H11ClN2O3.K/c17-10-6-7-12-11(8-10)13(9-4-2-1-3-5-9)19-14(16(21)22)15(20)18-12;/h1-8,14H,(H,18,20)(H,21,22);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017105s076lbl.pdf

Clorazepate is a water-soluble benzodiazepine derivative effective in the treatment of anxiety. It has also muscle relaxant and anticonvulsant actions. Studies in healthy men have shown that clorazepate dipotassium has depressant effects on the central nervous system. clorazepate is a prodrug since orally administered it is rapidly decarboxylated to form nordiazepam, there is essentially no circulating parent drug. Nordiazepam positively modulates GABAA receptors to produce anxiolytic and anticonvulsant effects.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 202 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18384456	Positive Allosteric Modulator 179

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 267 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017105s076lbl.pdf	Primary		Approved 8429	TRANXENE Approved Use TRANXENE is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. TRANXENE tablets are indicated as adjunctive therapy in the management of partial seizures. The effectiveness of TRANXENE tablets in long-term management of anxiety, that is, more than 4 months, has not been assessed by systematic clinical studies. Long-term studies in epileptic patients, however, have shown continued therapeutic activity. The physician should reassess periodically the usefulness of the drug for the individual patient. TRANXENE tablets are indicated for the symptomatic relief of acute alcohol withdrawal. CONTRAINDICATIONS TRANXENE tablets are contraindicated in patients with a known hypersensitivity to the drug and in those with acute narrow angle glaucoma. Launch Date 1972
Partial seizures 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017105s076lbl.pdf	Palliative		Approved 8429	TRANXENE Approved Use TRANXENE is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. TRANXENE tablets are indicated as adjunctive therapy in the management of partial seizures. The effectiveness of TRANXENE tablets in long-term management of anxiety, that is, more than 4 months, has not been assessed by systematic clinical studies. Long-term studies in epileptic patients, however, have shown continued therapeutic activity. The physician should reassess periodically the usefulness of the drug for the individual patient. TRANXENE tablets are indicated for the symptomatic relief of acute alcohol withdrawal. CONTRAINDICATIONS TRANXENE tablets are contraindicated in patients with a known hypersensitivity to the drug and in those with acute narrow angle glaucoma. Launch Date 1972

C_max

Value	Dose	Co-administered	Analyte	Population
245 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6119204/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		NORDAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
413 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6119204/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		NORDAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
187 μM × h/mL × kg EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29058/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: DIGOXIN	DIGOXIN	NORDAZEPAM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
230 μM × h/mL × kg EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29058/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: DIGOXIN	DIGOXIN	NORDAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Analyte	Population
2.291 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6137019/	20 mg single, intramuscular dose: 20 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	CLORAZEPIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6137019/	20 mg single, intravenous dose: 20 mg route of administration: Intravenous experiment type: SINGLE co-administered:	CLORAZEPIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
29.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6119204/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	NORDAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
54.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6119204/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	NORDAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
45.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6137019/	20 mg single, intramuscular dose: 20 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	NORDAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
46 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6137019/	20 mg single, intravenous dose: 20 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NORDAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 mg 1 times / day multiple, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/017105_S070_Tranxene_APPROVAL_PACKAGE.pdf	unhealthy, 9-12 years Health Status: unhealthy Age Group: 9-12 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/017105_S070_Tranxene_APPROVAL_PACKAGE.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/017105_S070_Tranxene_APPROVAL_PACKAGE.pdf
90 mg 1 times / day multiple, oral Recommended Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/017105_S070_Tranxene_APPROVAL_PACKAGE.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/017105_S070_Tranxene_APPROVAL_PACKAGE.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/017105_S070_Tranxene_APPROVAL_PACKAGE.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/017105s084lbl.pdf#page=2 Page: 2.0	yes

Sourcing

Vendor/Aggregator	ID	URL
AAA Chemistry	AR-1H3291
ABI Chem	AC1L1EIN
ABI Chem	AC1Q3S8C
Achemica	ACMC-20dcfi	http://www.achemica.com/prodinfo/?id=144878
Alfa Chemistry	ACM5991719
Alsachim	3036	http://www.alsachim.com/product-C4111-glo.bal-view.html
Angene	AGN-PC-0SN09T
ChemMol	99046672	http://www.chemmol.com/chemmol/99046672.html
ChemTik	CTK0H0237
Clearsynth	CS-CX-00252	https://www.clearsynth.com/en/CSCX00252.html
Compound Cloud	23691043
Compound Cloud	23706210
Compound Cloud	2809
MuseChem	I006167	https://www.musechem.com/product/I006167.html
MuseChem	M098100	https://www.musechem.com/product/M098100.html
Smolecule	S524049	http://www.smolecule.com/products/s524049
THE BioTek	bt-263910	https://www.thebiotek.com/product/inhibitors/bt-263910
Toronto Research Chemicals	C325250
Yick-Vic Chemicals & Pharmaceuticals (HK) Ltd.	PH-0651TA
ZINC	ZINC000028973441	http://zinc15.docking.org/substances/ZINC000028973441
ZINC	ZINC000028973446	http://zinc15.docking.org/substances/ZINC000028973446
eMolecules	225790947
eMolecules	50519523

PubMed

Title	Date	PubMed
Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines.	1980 Mar 29	7388368
Allosteric modulation by benzodiazepine receptor ligands of the GABAA receptor channel expressed in Xenopus oocytes.	1988 Jan	2448430
The effects of benzodiazepine use during pregnancy and lactation.	1994 Nov-Dec	7881198
[Acute intermittent porphyria revealed by a paradoxical reaction to a benzodiazepine].	2001 Aug-Sep	11598550
In vitro drug allergy detection system incorporating human liver microsomes in chlorazepate-induced skin rash: drug-specific proliferation associated with interleukin-5 secretion.	2001 Feb	11251565
Differences between the tolerance characteristics of two anticonvulsant benzodiazepines in the amygdaloid-kindled rat.	2001 Jul 20	11508647
Comparison of patient questionnaires, medical records, and plasma assays in assessing exposure to benzodiazepines in elderly subjects.	2001 Jun	11406742
Settlement plan approved for lorazepam, clorazepate overcharges.	2001 Jun 15	11449851
Very long half-life of paroxetine following intoxication in an extensive cytochrome P4502D6 metabolizer.	2002 Aug	12142644
[Investigations of poisonings with benzodiazepine derivatives mixtures by thin-layer chromatography].	2003	14646465
[Catatonia de novo, report on a case: immediate vital prognosis and psychiatric prognosis in longer term].	2003 Jan-Feb	12640330
[Voluntary poisoning by ingestion of Datura stramonium. Another cause of hospitalization in youth seeking strong sensations].	2003 Jun	12910033
[Can treatment associated with ticlopidine and nifedipine increase serum levels of phenobarbital?].	2003 Mar 1-15	12640596
[Benzodiazepine poisoning in a neonate: clinical and toxicokinetic evaluation following enterodialysis with activated charcoal].	2004 Jul	15234378
Acute and chronic administration of clorazepate modifies the cell surface regulation of mu opioid receptors induced by buprenorphine in specific regions of the rat brain.	2005 Aug 9	16023087
Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade.	2005 Feb	15289999
Clorazepate affects cell surface regulation of delta and kappa opioid receptors, thereby altering buprenorphine-induced adaptation in the rat brain.	2005 Nov 23	16269137
Repetitive transcranial magnetic stimulation (rTMS) in a patient suffering from comorbid depression and panic disorder following a myocardial infarction.	2006 Jul	16631291
[Psoriasis and anxiety: marked improvement after anxiolytic therapy].	2006 Sep	16956512
Piloerection induced by replacing fluvoxamine with milnacipran.	2007 Jun	17324248
Flumazenil-sensitive dose-related physical dependence in planarians produced by two benzodiazepine and one non-benzodiazepine benzodiazepine-receptor agonists.	2007 Jun 14	17368613
A rapid fluorimetric screening method for the 1,4-benzodiazepines: determination of their metabolite oxazepam in urine.	2007 May 15	17456431
[Abuse of alcohol and benzodiazepine during substitution therapy in heroin addicts: a review of the literature].	2009 Jun	19540407
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
[Tolerance of prostate biopsy with use of local anesthesia and benzodiazepines: a randomized, prospective study].	2010 Jan	20223132
Paradoxical reaction to midazolam reversed with flumazenil.	2010 Jul	20931003
Generalized skin drug eruption to natalizumab in a patient with multiple sclerosis.	2010 Jun 15	20579469
Blood concentrations of clobazam and norclobazam in a lethal case involving clobazam, meprobamate and clorazepate.	2010 Nov	20870445

Patents

Sample Use Guides

In Vivo Use Guide

For the symptomatic relief of anxiety: TRANXENE T-TAB tablets are administered orally in divided doses. The usual daily dose is 30 mg. The dose should be adjusted gradually within the range of 15 to 60 mg daily in accordance with the response of the patient. In elderly or debilitated patients it is advisable to initiate treatment at a daily dose of 7.5 to 15 mg. TRANXENE tablets may also be administered in a single dose daily at bedtime; the recommended initial dose is 15 mg. After the initial dose, the response of the patient may require adjustment of subsequent dosage. Lower doses may be indicated in the elderly patient. Drowsiness may occur at the initiation of treatment and with dosage increment. As an Adjunct to Antiepileptic Drugs: In order to minimize drowsiness, the recommended initial dosages and dosage increments should not be exceeded. Adults: The maximum recommended initial dose in patients over 12 years old is 7.5 mg three times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 90 mg/day. Children (9-12 years): The maximum recommended initial dose is 7.5 mg two times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 60 mg/day

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

CLORAZEPATE MONOPOTASSIUM

Official Name

English

Potassium 7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-carboxylate

Systematic Name

English

Clorazepate monopotassium [WHO-DD]

Common Name

English

CLORAZEPATE POTASSIUM

Common Name

English

CLORAZEPATE MONOPOTASSIUM [MART.]

Common Name

English

CLORAZEPATE MONOPOTASSIUM [USAN]

Common Name

English

1H-1,4-BENZODIAZEPINE-3-CARBOXYLIC ACID, 7-CHLORO-2,3-DIHYDRO-2-OXO-5-PHENYL-, POTASSIUM SALT

Systematic Name

English

ABBOTT-39083

Code

English

CLORAZEPIC ACID MONOPOTASSIUM SALT

Common Name

English

4311-CB

Code

English

CLORAZEPIC ACID MONOPOTASSIUM SALT [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1012