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Identification
NameProgabide
Accession NumberDB00837  (APRD00072)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Progabide is an analog and prodrug of gamma-aminobutyric acid. It is commonly used in the treatment of epilepsy. It has agonistic activity for both the GABAA and GABAB receptors. Progabide has been investigated for many diseases besides epilepsy, including Parkinson’s disease, schizophrenia, clinical depression and anxiety disorder with varying success.

Structure
Thumb
Synonyms
SynonymLanguageCode
HalogabideNot AvailableNot Available
ProgabidaSpanishINN
ProgabideNot AvailableINN, BAN, USAN
ProgabidumLatinINN
SaltsNot Available
Brand names
NameCompany
GabrenNot Available
GabreneSanofi S.A.
Brand mixturesNot Available
Categories
CAS number62666-20-0
WeightAverage: 334.773
Monoisotopic: 334.088433678
Chemical FormulaC17H16ClFN2O2
InChI KeyDWEQWXSKOHHBNT-SAPNQHFASA-N
InChI
InChI=1S/C17H16ClFN2O2/c18-12-5-3-11(4-6-12)17(21-9-1-2-16(20)23)14-10-13(19)7-8-15(14)22/h3-8,10,21H,1-2,9H2,(H2,20,23)/b17-14+
IUPAC Name
4-{[(4-chlorophenyl)[(1E)-3-fluoro-6-oxocyclohexa-2,4-dien-1-ylidene]methyl]amino}butanamide
SMILES
NC(=O)CCCN\C(C1=CC=C(Cl)C=C1)=C1/C=C(F)C=CC1=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentGamma Amino Acids and Derivatives
Alternative parentso-Quinomethanes; Chlorobenzenes; Aryl Chlorides; Primary Carboxylic Acid Amides; Enolates; Polyamines; Carboxylic Acids; Enamines; Organofluorides; Organochlorides
Substituentso-quinomethane; quinomethane; chlorobenzene; aryl chloride; aryl halide; benzene; carboxamide group; primary carboxylic acid amide; ketone; carboxylic acid; enolate; enamine; polyamine; organofluoride; organochloride; organohalogen; carbonyl group; amine; organonitrogen compound
Classification descriptionThis compound belongs to the gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
Pharmacology
IndicationIndicated for the treatment of epilepsy.
PharmacodynamicsProgabide, a fatty acid derivative, is a GABA receptor agonist used to treat the symptoms of epilepsy.
Mechanism of actionProgabide binds to both GABAA and GABAB receptors located on the terminals of primary afferent fibers. Binding to GABAA results in an increased affinity of the GABA receptor for the amino acid, an augmented flux of chloride ions across the terminal membrane, and an increase in the amount of presynaptic inhibition. Activation of the GABAB receptors retards the influx of calcium ions into the terminals, thereby reducing the evoked release of excitatory amino acids and possibly other transmitters.
AbsorptionWell absorbed with a bioavailability of 60%
Volume of distributionNot Available
Protein binding95%
Metabolism

Hepatic

Route of eliminationNot Available
Half life4 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9959
Blood Brain Barrier + 0.9534
Caco-2 permeable + 0.5085
P-glycoprotein substrate Substrate 0.5433
P-glycoprotein inhibitor I Inhibitor 0.8381
P-glycoprotein inhibitor II Non-inhibitor 0.9194
Renal organic cation transporter Non-inhibitor 0.6
CYP450 2C9 substrate Non-substrate 0.8307
CYP450 2D6 substrate Non-substrate 0.7538
CYP450 3A4 substrate Substrate 0.5797
CYP450 1A2 substrate Inhibitor 0.507
CYP450 2C9 substrate Non-inhibitor 0.5455
CYP450 2D6 substrate Non-inhibitor 0.7138
CYP450 2C19 substrate Inhibitor 0.6943
CYP450 3A4 substrate Inhibitor 0.6492
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8101
Ames test Non AMES toxic 0.567
Carcinogenicity Non-carcinogens 0.8525
Biodegradation Not ready biodegradable 0.9803
Rat acute toxicity 2.4097 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8492
hERG inhibition (predictor II) Inhibitor 0.5546
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point133-135 °CPhysProp
water solubility70.9 mg/LNot Available
logP3.06FARRAJ,NF ET AL. (1988)
Predicted Properties
PropertyValueSource
Water Solubility0.00442ALOGPS
logP2.68ALOGPS
logP1.8ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)15.32ChemAxon
pKa (Strongest Basic)4.01ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.19 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity91.22 m3·mol-1ChemAxon
Polarizability33.21 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Bartholini G, Scatton B, Zivkovic B, Lloyd KG: GABA receptor agonists and extrapyramidal motor function: therapeutic implications for Parkinson’s disease. Adv Neurol. 1987;45:79-83. Pubmed
External Links
ResourceLink
KEGG DrugD05621
PubChem Compound5361323
PubChem Substance46506568
ChemSpider4514729
Therapeutic Targets DatabaseDAP000258
PharmGKBPA164747990
WikipediaProgabide
ATC CodesN03AG05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Gamma-aminobutyric acid type B receptor subunit 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid type B receptor subunit 1 Q9UBS5 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Agmo A, Belzung C: Interactions between dopamine and GABA in the control of ambulatory activity and neophobia in the mouse. Pharmacol Biochem Behav. 1998 Jan;59(1):239-47. Pubmed
  3. Fadda F, Mosca E, Meloni R, Gessa GL: Suppression by progabide of ethanol withdrawal syndrome in rats. Eur J Pharmacol. 1985 Mar 12;109(3):321-5. Pubmed

2. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Agmo A, Belzung C: Interactions between dopamine and GABA in the control of ambulatory activity and neophobia in the mouse. Pharmacol Biochem Behav. 1998 Jan;59(1):239-47. Pubmed
  4. Grech DM, Balster RL: Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats. Psychopharmacology (Berl). 1993;110(3):295-301. Pubmed
  5. Fadda F, Mosca E, Meloni R, Gessa GL: Suppression by progabide of ethanol withdrawal syndrome in rats. Eur J Pharmacol. 1985 Mar 12;109(3):321-5. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 27, 2013 18:24