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Identification
NameProgabide
Accession NumberDB00837  (APRD00072)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionProgabide 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
Halogabide
Progabida
Progabide
Progabidum
External Identifiers
  • SL 76 002
  • SL-76002
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
GabrenNot Available
GabreneSanofi S.A.
Brand mixturesNot Available
SaltsNot Available
Categories
UNII38C836J57Z
CAS number62666-20-0
WeightAverage: 334.78
Monoisotopic: 334.0884336
Chemical FormulaC17H16ClFN2O2
InChI KeyIBALRBWGSVJPAP-FXBPSFAMSA-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/h3-8,10,22H,1-2,9H2,(H2,20,23)/b21-17-
IUPAC Name
4-[(Z)-[(4-chlorophenyl)(5-fluoro-2-hydroxyphenyl)methylidene]amino]butanimidic acid
SMILES
OC(=N)CCC\N=C(\C1=CC=C(Cl)C=C1)C1=C(O)C=CC(F)=C1
Pharmacology
IndicationIndicated for the treatment of epilepsy.
Structured Indications Not Available
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Gamma-aminobutyric acid receptor subunit alpha-1Proteinyes
agonist
HumanP14867 details
Gamma-aminobutyric acid type B receptor subunit 1Proteinyes
agonist
HumanQ9UBS5 details
Related Articles
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
Interactions
Drug Interactions
DrugInteractionDrug group
MefloquineThe therapeutic efficacy of Progabide can be decreased when used in combination with Mefloquine.Approved
MianserinThe therapeutic efficacy of Progabide can be decreased when used in combination with Mianserin.Approved
OrlistatThe serum concentration of Progabide can be decreased when it is combined with Orlistat.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  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:3030072 ]
External Links
ATC CodesN03AG05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9959
Blood Brain Barrier+0.9534
Caco-2 permeable+0.5085
P-glycoprotein substrateSubstrate0.5433
P-glycoprotein inhibitor IInhibitor0.8381
P-glycoprotein inhibitor IINon-inhibitor0.9194
Renal organic cation transporterNon-inhibitor0.6
CYP450 2C9 substrateNon-substrate0.8307
CYP450 2D6 substrateNon-substrate0.7538
CYP450 3A4 substrateSubstrate0.5797
CYP450 1A2 substrateInhibitor0.507
CYP450 2C9 inhibitorNon-inhibitor0.5455
CYP450 2D6 inhibitorNon-inhibitor0.7138
CYP450 2C19 inhibitorInhibitor0.6943
CYP450 3A4 inhibitorInhibitor0.6492
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8101
Ames testNon AMES toxic0.567
CarcinogenicityNon-carcinogens0.8525
BiodegradationNot ready biodegradable0.9803
Rat acute toxicity2.4097 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8492
hERG inhibition (predictor II)Inhibitor0.5546
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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 Solubility0.00552 mg/mLALOGPS
logP3.22ALOGPS
logP1.47ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)-1.1ChemAxon
pKa (Strongest Basic)12ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area76.67 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity98.89 m3·mol-1ChemAxon
Polarizability33.53 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
ClassificationNot classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By si...
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
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:17139284 ]
  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:17016423 ]
  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:9443561 ]
  4. Grech DM, Balster RL: Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats. Psychopharmacology (Berl). 1993;110(3):295-301. [PubMed:7831422 ]
  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:2985405 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
G-protein coupled gaba receptor activity
Specific Function:
Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such a...
Gene Name:
GABBR1
Uniprot ID:
Q9UBS5
Molecular Weight:
108319.4 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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:9443561 ]
  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:2985405 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23