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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 of MEPROBAMATE

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

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 Meprobamate was withdrawn from European and Canadian markets due to its potential to cause physical and psychological dependence.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 TargetPharmacologyConditionPotency
55.0 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MILTOWN

Cmax

ValueDoseCo-administeredAnalytePopulation
1.8 μg/mL
250 mg single, oral
MEPROBAMATE plasma
Homo sapiens
2.5 μg/mL
350 mg single, oral
MEPROBAMATE plasma
Homo sapiens
18.4 μM
700 mg single, oral
MEPROBAMATE serum
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
32 μg × h/mL
250 mg single, oral
MEPROBAMATE plasma
Homo sapiens
46 μg × h/mL
350 mg single, oral
MEPROBAMATE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
9.7 h
250 mg single, oral
MEPROBAMATE plasma
Homo sapiens
9.6 h
350 mg single, oral
MEPROBAMATE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
76%
700 mg single, oral
MEPROBAMATE serum
Homo sapiens

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

PubMed

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.