Barbexaclone

Identification

Generic Name

Barbexaclone

DrugBank Accession Number

DB09001

Background

Barbexaclone, a salt compound of propylhexedrine and phenobarbital, is a potent antiepileptic. By weight, barbexaclone is 40% propylhexedrine and 60% phenobarbital. While barbexaclone has sedative properties, propylhexedrine has psychostimulant properties intended to offset these sedative effects. Pharmacokinetic studies have demonstrated that the pharmacokinetics of phenobarbital given as barbexaclone are not affected by propylhexedrine. Several reports from Spanish and Italian literature suggest that barbexaclone is at least as effective as phenobarbital in adults and children, while being better tolerated and having less sedative properties. These reports were conducted in a small series of patients in the 1970s and 1980s, and have yet to be confirmed by larger controlled trials. Despite the lack of controlled trials, barbexaclone was used widely in Turkey until it was discontinued in 2009.

Barbexaclone exists in 25mg and 100mg tablets. 100mg of barbexaclone is equivalent to 60mg of phenobarbital. With this difference in potency in mind, other pharmacokinetic considerations such as dose titration, daily dosing, and optimal plasma concentration can be considered the same as for the equivalent amount of phenobarbital.

There has been a case of barbexaclone abuse due to the amphetamine like properties of propylhexedrine, although the comparative abuse potential is much lower than amphetamine.

Type

Small Molecule

Groups

Experimental

Structure

Similar Structures

Weight: Average: 387.524
Monoisotopic: 387.252191935
Chemical Formula: C₂₂H₃₃N₃O₃

Synonyms

Barbexaclon
Barbexaclona
Barbexaclone
Barbexaclonum

External IDs

Su 42

Pharmacology

Indication: Created for the treatment for epilepsy, with the intent of creating an antiepileptic with less sedative properties than phenobarbital.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings: Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics: Not Available
Mechanism of action: Phenobarbitol targets GABA receptors in the CNS. Propylhexedrine is a TAAR1 agonist.
Absorption: After oral administration of barbexaclone in mice the maximum plasma levels of prophylhexedrine appeared after 4 minutes, and propylhexedrine was seen to penetrate the blood brain barrier rapidly. Bioavailability (AUC oral / AUC iv) = 0.37. [3] Phenobarbital was observed to reach the blood more slowly, and brain uptake was a slow process. Equilibrium concentrations with plasma reached after 30 minutes after i.v injection. [3]
Volume of distribution: In mice, the volume of distribution was 0.78L/kg of phenobarbital, and 19.3L/kg for propylhexedrine, after i.v. administration. [3] High but unequal tissue accumulation of propylhexedrine was observed in mice: lung = kidney > liver = brain > spleen > heart > skeletal muscle. [3]
Protein binding: Not Available
Metabolism: Not Available
Route of elimination: Not Available
Half-life: After IV administration in mice, levels of phenobarbital declined exponentially with a half life of 7.5h. [3] For propylhexedrine t0.5a = 0.31h and t0.5b = 2.5h.
Clearance: Not Available
Adverse Effects: Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity: Barbiturates are associated with congenital heart malformations, facial clefts, and other malformations. [5] There is no available data on the use of barbexaclone in pregnancy. One case of a 36 year old women who used barbexaclone 300mg/day and oxcarbezine 600mg/day for 2 years before the pregnancy and 10 weeks into pregnancy resulted in an uncomplicated delivery and normal physical, motor, and mental development at 24 months of age. [5]
Pathways: Not Available
Pharmacogenomic Effects/ADRs: Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Integrate drug-drug interactions in your software
1,2-Benzodiazepine	The risk or severity of CNS depression can be increased when Barbexaclone is combined with 1,2-Benzodiazepine.
Abaloparatide	Barbexaclone may increase the hypotensive activities of Abaloparatide.
Abemaciclib	The metabolism of Abemaciclib can be increased when combined with Barbexaclone.
Acalabrutinib	The metabolism of Acalabrutinib can be increased when combined with Barbexaclone.
Acebutolol	Barbexaclone may increase the hypotensive activities of Acebutolol.
Acenocoumarol	The metabolism of Acenocoumarol can be increased when combined with Barbexaclone.
Acetaminophen	The metabolism of Acetaminophen can be increased when combined with Barbexaclone.
Acetazolamide	The risk or severity of CNS depression can be increased when Acetazolamide is combined with Barbexaclone.
Acetophenazine	The risk or severity of CNS depression can be increased when Acetophenazine is combined with Barbexaclone.
Agomelatine	The risk or severity of CNS depression can be increased when Agomelatine is combined with Barbexaclone.

Identify potential medication risks

Easily compare up to 40 drugs with our drug interaction checker.

Get severity rating, description, and management advice.

Learn more

Food Interactions

Not Available

Products

: Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands: Maliasin (Abbott)

Chemical Identifiers

UNII: 291GX1YB65
CAS number: 4388-82-3
InChI Key: MJCBWPMBFCUHBP-NPULLEENSA-N
InChI: InChI=1S/C12H12N2O3.C10H21N/c1-2-12(8-6-4-3-5-7-8)9(15)13-11(17)14-10(12)16;1-9(11-2)8-10-6-4-3-5-7-10/h3-7H,2H2,1H3,(H2,13,14,15,16,17);9-11H,3-8H2,1-2H3/t;9-/m.0/s1
IUPAC Name: 5-ethyl-5-phenyl-1,3-diazinane-2,4,6-trione; [(2S)-1-cyclohexylpropan-2-yl](methyl)amine
SMILES: CN[C@@H](C)CC1CCCCC1.CCC1(C(=O)NC(=O)NC1=O)C1=CC=CC=C1

References

General References

Bolukbasi F, Delil S, Bulus E, Senturk A, Yeni N, Karaagac N: End of the barbexaclone era: an experience of treatment withdrawal. Epileptic Disord. 2013 Sep;15(3):311-3. doi: 10.1684/epd.2013.0605. [Article]
Iven H, Feldbusch E: Pharmacokinetics of phenobarbital and propylhexedrine after administration of barbexaclone in the mouse. Naunyn Schmiedebergs Arch Pharmacol. 1983 Sep;324(2):153-9. [Article]
Yaris F, Kadioglu M, Kesim M, Ulku C, Yaris E, Kalyoncu NI: Barbexaclone use in pregnancy. Saudi Med J. 2004 Feb;25(2):245-6. [Article]
Shorvon, Simon D.;Dodson, W. E.;Fish, David;Perucca, Emilio;Aminoff, Michael J. (2004). The Treatment of Epilepsy (2nd ed.). John Wiley & Sons. [ISBN:0-632-06046-8]

External Links

PubChem Compound: 71196
PubChem Substance: 347827816
ChemSpider: 64332
RxNav: 46795
Drugs.com: Drugs.com Drug Page
Wikipedia: Barbexaclone

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet, coated

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.276 mg/mL	ALOGPS
logP	1.4	ALOGPS
logP	1.41	Chemaxon
logS	-2.9	ALOGPS
pKa (Strongest Acidic)	7.14	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	3	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	75.27 Å²	Chemaxon
Rotatable Bond Count	5	Chemaxon
Refractivity	59.75 m³·mol^-1	Chemaxon
Polarizability	22.61 Å³	Chemaxon
Number of Rings	3	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Drug created at June 17, 2014 16:50 / Updated at February 21, 2021 18:52

Barbexaclone

Identification

Structure for Barbexaclone (DB09001)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra