MEPROBAMATE

First approved in 1955

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H18N2O4
Molecular Weight	218.2502
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC(C)(COC(N)=O)COC(N)=O

InChI

InChIKey=NPPQSCRMBWNHMW-UHFFFAOYSA-N

InChI=1S/C9H18N2O4/c1-3-4-9(2,5-14-7(10)12)6-15-8(11)13/h3-6H2,1-2H3,(H2,10,12)(H2,11,13)

HIDE SMILES / InChI

Molecular Formula	C9H18N2O4
Molecular Weight	218.2502
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugs.com/monograph/meprobamate.html
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9067327 | https://www.ncbi.nlm.nih.gov/pubmed/6128137 | http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/meprobamate_107/WC500120737.pdf

Meprobamate is a carbamate derivative used as an anxiolytic drug. Meprobamate enhances GABA-A currents, and at higher concentration, exhibits a separate channel-blocking effect that limits the magnitude of GABA(A) receptor potentiation. It is also a potent adenosine reuptake inhibitor (AdoRI), which is most likely responsible for its lesser degree of sedation compared to barbiturates. Meprobamate was withdrawn from European and Canadian markets due to its potential to cause physical and psychological dependence.

CNS Activity

Originator

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/9067327	Activator 1410
Equilibrative nucleoside transporter 1 7 Target ID: CHEMBL1997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6128137	Inhibitor 8228		55.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 266 Sources: https://www.drugs.com/pro/meprobamate.html	Primary		Approved 8360	MILTOWN Approved Use Meprobamate tablets are 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 do not require treatment with an anxiolytic. The effectiveness of meprobamate tablets in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient. Launch Date -4.63276802E11

C_max

Value	Dose	Analyte	Population
1.8 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011792s048lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	MEPROBAMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.5 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011792s048lbl.pdf	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:	MEPROBAMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18.4 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7974621	700 mg single, oral dose: 700 mg route of administration: Oral experiment type: SINGLE co-administered:	MEPROBAMATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
32 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011792s048lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		MEPROBAMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
46 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011792s048lbl.pdf	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:		MEPROBAMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011792s048lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		MEPROBAMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011792s048lbl.pdf	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:		MEPROBAMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
76% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7974621	700 mg single, oral dose: 700 mg route of administration: Oral experiment type: SINGLE co-administered:		MEPROBAMATE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 985

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C19 985	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/books/NBK425390/	yes		likely (co-administration study) Comment: co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, could result in increased exposure of carisoprodol and decreased exposure of meprobamate Sources: https://www.ncbi.nlm.nih.gov/books/NBK425390/

Sourcing

Vendor/Aggregator	ID	URL
Achemtek	0104-020240	http://www.achemtek.com/57-53-4
Alsachim	1520	http://www.alsachim.com/product-C2765-glo.bal-view.html
Aurora Fine Chemicals LLC	A17.878.279	http://online.aurorafinechemicals.com/info?ID=A17.878.279
Avantor Inc	75835-930	https://us.vwr.com/store/product/21998648/exempted-drug-of-abuse-reference-standards-restek
BioSynth	W-105461	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-105461.html
ChemMol	49416390	http://www.chemmol.com/chemmol/49416390.html
Clearsynth	CS-EB-01302	https://www.clearsynth.com/en/CSEB01302.html
Clearsynth	CS-ER-01294	https://www.clearsynth.com/en/CSER01294.html
LGC Standards	LGCAMP0929.00-01	https://www.lgcstandards.com/US/en/p/LGCAMP0929.00-01
LGC Standards	LGCFOR0929.00	https://www.lgcstandards.com/US/en/p/LGCFOR0929.00
LGC Standards	MM0929.00	https://www.lgcstandards.com/US/en/p/MM0929.00
MuseChem	I007956	https://www.musechem.com/product/I007956.html
OChem	8503	http://www.ocheminc.com/index.php?act=psearch&pid=063M428
Sigma-Aldrich	M-039_CERILLIAN	https://www.sigmaaldrich.com/catalog/product/cerillian/m039?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	M0400000_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/m0400000?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	M2392_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/m2392?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	M0271_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/m0271?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1389008_USP	https://www.sigmaaldrich.com/catalog/product/usp/1389008?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S534989	http://www.smolecule.com/products/s534989
Synthink Research Chemicals	SA25301	https://synthinkchemicals.com/product/carisoprodol-ep-impurity-d-meprobamate/
THE BioTek	bt-274767	https://www.thebiotek.com/product/inhibitors/bt-274767

PubMed

Title	Date	PubMed
THE ACTION OF SODIUM 4-HYDROXYBUTYRATE ON SPINAL REFLEXES.	1964 Apr	14190466
Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity.	2001 Apr 20	11278902
The fate of neurotization techniques on reinnervation after denervation of the gastrocnemius muscle: an experimental study.	2001 Jul	11499469
Accuracy and precision of computer models to predict passage of crude protein and amino acids to the duodenum of lactating cows.	2001 Mar	11286419
Focusing on the genetics of hearing: you ain't heard nothin' yet.	2002	12093367
Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.	2002 Dec 16	12485990
Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness.	2002 Jul	12136232
Mast cells in the pathogenesis of chronic back pain: a hypothesis.	2002 Jul	12115872
The projections of early enteric neurons are influenced by the direction of neural crest cell migration.	2002 Jul 15	12122062
Zinc ligands in an astacin family metalloprotease meprin A.	2002 Jul-Aug	12437102
Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC.	2002 Jun	12107438
Defective assembly of sarcoglycan complex in patients with beta-sarcoglycan gene mutations. Study of aneural and innervated cultured myotubes.	2002 Jun	12060343
The new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers.	2002 Oct 23	12387856
A selective interaction between OS-9 and the carboxyl-terminal tail of meprin beta.	2002 Sep 13	12093806
Meprin proteolytic complexes at the cell surface and in extracellular spaces.	2003	14587282
Functional analysis of an arthritogenic synovial fibroblast.	2003	12723986
Degeneration of the intervertebral disc.	2003	12723977
A need for a 'whole-istic functional genomics' approach in complex human diseases: arthritis.	2003	12718747
Expression of meprins in health and disease.	2003	12696749
Modification of the transcriptomic response to renal ischemia/reperfusion injury by lipoxin analog.	2003 Aug	12846743
Mouse models of USH1C and DFNB18: phenotypic and molecular analyses of two new spontaneous mutations of the Ush1c gene.	2003 Dec 1	14519688
Human meprin beta: O-linked glycans in the intervening region of the type I membrane protein protect the C-terminal region from proteolytic cleavage and diminish its secretion.	2003 Feb 1	12387727
Association between blood carisoprodol:meprobamate concentration ratios and CYP2C19 genotype in carisoprodol-drugged drivers: decreased metabolic capacity in heterozygous CYP2C191/CYP2C192 subjects?	2003 Jul	12835613
The molecular genetics of Usher syndrome.	2003 Jun	12786748
MRF4 gene expression in Xenopus embryos and aneural myofibers.	2003 Mar	12619139
Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin.	2003 Mar 1	12588794
Differences in the activation mechanism between the alpha and beta subunits of human meprin.	2003 May	12817480
[Adjuvant therapy with parenteral piracetam in alcohol withdrawal delirium].	2003 May 11	12809069
Differential distribution of harmonin isoforms and their possible role in Usher-1 protein complexes in mammalian photoreceptor cells.	2003 Nov	14578428
Critical amino acids in the active site of meprin metalloproteinases for substrate and peptide bond specificity.	2003 Oct 24	12888571
In vivo mucosal delivery of bioactive human interleukin 1 receptor antagonist produced by Streptococcus gordonii.	2003 Sep 17	13129437
Morphology of brachial segments in mudpuppy (Necturus maculosus) spinal cord studied with confocal and electron microscopy.	2004 Apr 5	14991567
Transport of meprin subunits through the secretory pathway: role of the transmembrane and cytoplasmic domains and oligomerization.	2004 Aug 13	15187079
Structure, diversity, and evolution of the 45-bp VNTR in intron 5 of the USH1C gene.	2004 Mar	14962669
Human meprin alpha and beta homo-oligomers: cleavage of basement membrane proteins and sensitivity to metalloprotease inhibitors.	2004 Mar 1	14594449
Aneural culture of rat myoblasts for myocardial transplant.	2004 May	15194356
Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein that interacts with harmonin in epithelial tissues.	2004 Oct	15461667
Genetic heterogeneity in Usher syndrome.	2004 Sep 15	15368488
Sequence and structural analysis of BTB domain proteins.	2005	16207353
Inhibitors of polyamine biosynthesis decrease the expression of the metalloproteases meprin alpha and MMP-7 in hormone-independent human breast cancer cells.	2005	16170669
Metastasis of hormone-independent breast cancer to lung and bone is decreased by alpha-difluoromethylornithine treatment.	2005	16168128
Indigo carmine for the selective endoscopic intervertebral nuclectomy.	2005 Aug	16100472
A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.	2005 Dec	16283141
Meprin metalloprotease expression and regulation in kidney, intestine, urinary tract infections and cancer.	2005 Jun 13	15943977
Expression and genomic organization of zonadhesin-like genes in three species of fish give insight into the evolutionary history of a mosaic protein.	2005 Nov 22	16303057
Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations.	2005 Oct	16162647
Meprin beta metalloprotease gene polymorphisms associated with diabetic nephropathy in the Pima Indians.	2005 Oct	16133184
Meprin-alpha in chronic diabetic nephropathy: interaction with the renin-angiotensin axis.	2005 Oct	15942051
Usher I syndrome: unravelling the mechanisms that underlie the cohesion of the growing hair bundle in inner ear sensory cells.	2005 Oct 15	16219682
Mannan-binding protein blocks the activation of metalloproteases meprin alpha and beta.	2005 Sep 1	16116208

Patents

Sample Use Guides

In Vivo Use Guide

Meprobamate is administered orally. The smallest effective individual doses should be used to avoid oversedation. Typical dose is 1.2–1.6 g daily in 3 or 4 divided doses.

Route of Administration: Oral

In Vitro Use Guide

All electrophysiological recordings were conducted on the stage of a Nikon Diaphot inverted phase contrast microscope at room temperature (23–25°C). Currents were monitored with either an Axopatch 1B or 200A patch clamp amplifier. Voltages corresponding to the currents were acquired with a high-speed chart recorder, and digitized for off-line analysis with the Axotape software package. The holding potential for whole-cell recordings was −60 mV unless otherwise noted. Drugs were dissolved in buffer on the day of use and applied via a nine-barrel rapid perfusion system in which all barrels (320 μm outer diameter quartz tubes; J & W Scientific, Folsom, CA) emptied via a common tip positioned within 200 μm from the tip of the patch electrode in excised patch recordings and 400 μm from the cell under study in whole-cell recordings. Flow through each barrel was gravity fed and regulated by high-speed solenoid microvalves (The Lee Co., Westbrook, CT) operated by a programmable microprocessor-based controller. Switching between solutions occurred within <10 ms (seeDonevan et al., 1992). One barrel contained buffer and the others were filled with various drugs alone and in combination. Only one valve was open at a time, and the buffer solution was applied continuously between drug applications. In the single-channel recordings, drugs were applied for 15- to 60-s epochs, separated by 30- to 60-s wash periods. In whole-cell voltage-clamp recordings from cultured rat hippocampal neurons, meprobamate enhanced GABA-evoked responses in a concentration-dependent manner with EC50 of 1.2 mM.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 22:50:56 UTC 2023` Edited by `admin` on `Wed Jul 05 22:50:56 UTC 2023`
Record UNII	9I7LNY769Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MEPROBAMATE

Official Name

English

MEPRIAM

Brand Name

English

Q-GESIC COMPONENT MEPROBAMATE

Common Name

English

MEPROBAMATE [JAN]

Common Name

English

EQUAGESIC COMPONENT MEPROBAMATE

Common Name

English

BAMATE

Brand Name

English

EQUANIL

Brand Name

English

MICRAININ COMPONENT MEPROBAMATE

Common Name

English

TRANMEP

Brand Name

English

MEPROBAMATE [USP MONOGRAPH]

Common Name

English

Meprobamate [WHO-DD]

Common Name

English

MEPROBAMATE COMPONENT OF EQUAGESIC

Common Name

English

MEPROBAMATE [VANDF]

Common Name

English

AMOSENE

Brand Name

English

NSC-30418

Code

English

MEPROSPAN

Brand Name

English

MEPROBAMATE COMPONENT OF Q-GESIC

Common Name

English

MEPROBAMATE CIV [USP-RS]

Common Name

English

MEPROBAMATE [MI]

Common Name

English

MEPROBAMATE [HSDB]

Common Name

English

MILTOWN

Brand Name

English

MEPROBAMATE [ORANGE BOOK]

Common Name

English

2-Methyl-2-propyl-1,3-propanediol dicarbamate

Systematic Name

English

1,3-PROPANEDIOL, 2-METHYL-2-PROPYL-, DICARBAMATE

Systematic Name

English

meprobamate [INN]

Common Name

English

MEPROBAMATE [EP IMPURITY]

Common Name

English

MEPROBAMATE [MART.]

Common Name

English

MEPRO-ASPIRIN COMPONENT MEPROBAMATE

Common Name

English

MEPROBAMATE COMPONENT OF MICRAININ

Common Name

English

NEURAMATE

Brand Name

English

MEPROBAMATE COMPONENT OF MEPRO-ASPIRIN

Common Name

English

MEPROBAMATE CIV

Common Name

English

Classification Tree Code System Code

WHO-VATC

QN05CX01