MEPROBAMATE

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

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 Meprobamate was withdrawn from European and Canadian markets due to its potential to cause physical and psychological dependence.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 1430
Equilibrative nucleoside transporter 1 7 Target ID: CHEMBL1997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6128137	Inhibitor 8297		55.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 267 Sources: https://www.drugs.com/pro/meprobamate.html	Primary		Approved 8429	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 1955

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 991

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C19 991	substrate 3367 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
Usher syndrome: from genetics to pathogenesis.	2001	11701652
Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.	2001	11139240
Implementation of pretravel advice: good for malaria, bad for diarrhoea.	2001 Sep-Oct	11770223
The political, legal, and financial issues that plastic surgery is facing and how to develop a plan to cope.	2002 Jan	11827366
Methylation status of oestrogen receptor-alpha gene promoter sequences in human ovarian epithelial cell lines.	2002 Jan 21	11870520
Fgf4 positively regulates scleraxis and tenascin expression in chick limb tendons.	2002 Jul 15	12086472
Defective assembly of sarcoglycan complex in patients with beta-sarcoglycan gene mutations. Study of aneural and innervated cultured myotubes.	2002 Jun	12060343
The Woodard and Sowell (2001) study adds to the body of nursing knowledge that supports spirituality as a concept that I believe is relevant to nursing practice.	2002 May	11991168
The new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers.	2002 Oct 23	12387856
Activation of human meprin-alpha in a cell culture model of colorectal cancer is triggered by the plasminogen-activating system.	2002 Oct 25	12189145
Meprin proteolytic complexes at the cell surface and in extracellular spaces.	2003	14587282
Functional analysis of an arthritogenic synovial fibroblast.	2003	12723986
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
Receptor protein tyrosine phosphatase mu expression as a marker for endothelial cell heterogeneity; analysis of RPTPmu gene expression using LacZ knock-in mice.	2003 Jun	12895029
The molecular genetics of Usher syndrome.	2003 Jun	12786748
MRF4 gene expression in Xenopus embryos and aneural myofibers.	2003 Mar	12619139
Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26).	2003 Nov	13680526
Critical amino acids in the active site of meprin metalloproteinases for substrate and peptide bond specificity.	2003 Oct 24	12888571
Phorbol 12-myristate 13-acetate-induced ectodomain shedding and phosphorylation of the human meprinbeta metalloprotease.	2003 Oct 31	12941954
Deletion of the mouse meprin beta metalloprotease gene diminishes the ability of leukocytes to disseminate through extracellular matrix.	2004 Apr 1	15034068
Urinary meprin-alpha: a potential marker of diabetic nephropathy.	2004 Dec	15645700
Kinetics and rhythm of body contractions in the sponge Tethya wilhelma (Porifera: Demospongiae).	2004 Dec	15579547
HTLV-1 and -2 envelope SU subdomains and critical determinants in receptor binding.	2004 Dec 2	15575958
Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein that interacts with harmonin in epithelial tissues.	2004 Oct	15461667
Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo.	2005	15743499
The molecular immunology of mucositis: implications for evidence-based research in alternative and complementary palliative treatments.	2005 Dec	16322806
Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells.	2005 Dec 15	16301217
Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2.	2005 Dec 15	16301216
Interactions in the network of Usher syndrome type 1 proteins.	2005 Feb 1	15590703
Gene expression in the brain and kidney of rainbow trout in response to handling stress.	2005 Jan 6	15634361
Stimulation of poliovirus RNA synthesis and virus maturation in a HeLa cell-free in vitro translation-RNA replication system by viral protein 3CDpro.	2005 Nov 21	16300678
Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations.	2005 Oct	16162647
Analysis of prion strains by PrPSc profiling in sporadic Creutzfeldt-Jakob disease.	2006 Feb	16354106

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.

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