Progabide

Identification

Name
Progabide
Accession Number
DB00837
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. In clinical trials, progabide has been investigated for Parkinson's disease, schizophrenia, clinical depression and anxiety disorder; its therapeutic effectiveness in these conditions is not fully elucidated.

Type
Small Molecule
Groups
Experimental
Structure
Thumb
Weight
Average: 334.78
Monoisotopic: 334.0884336
Chemical Formula
C17H16ClFN2O2
Synonyms
  • Halogabide
  • Progabida
  • Progabide
  • Progabidum
External IDs
  • SL 76 002
  • SL 76002
  • SL-76002

Pharmacology

Indication

Indicated for the treatment of epilepsy.

Contraindications & Blackbox Warnings
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Pharmacodynamics

Progabide, a fatty acid derivative, is a GABA receptor agonist used to treat the symptoms of epilepsy.

Mechanism of action

Progabide 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.

TargetActionsOrganism
AGamma-aminobutyric acid type B receptor subunit 1
agonist
Humans
AGamma-aminobutyric acid receptor subunit alpha-1
agonist
Humans
Absorption

Well absorbed with a bioavailability of 60%

Volume of distribution
Not Available
Protein binding

95%

Metabolism

Hepatic

Route of elimination
Not Available
Half-life

4 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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.
DrugInteraction
AcenocoumarolThe risk or severity of adverse effects can be increased when Progabide is combined with Acenocoumarol.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Progabide.
AcetophenazineThe risk or severity of adverse effects can be increased when Progabide is combined with Acetophenazine.
AclidiniumProgabide may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Progabide is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Progabide.
AlimemazineThe risk or severity of adverse effects can be increased when Progabide is combined with Alimemazine.
AlmotriptanThe risk or severity of adverse effects can be increased when Progabide is combined with Almotriptan.
AlosetronThe risk or severity of adverse effects can be increased when Progabide is combined with Alosetron.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Progabide.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

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International/Other Brands
Gabren / Gabrene (Sanofi S.A.)

Categories

ATC Codes
N03AG05 — Progabide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
P-fluorophenols / Fluorobenzenes / Chlorobenzenes / 1-hydroxy-2-unsubstituted benzenoids / Aryl fluorides / Aryl chlorides / Secondary ketimines / Azomethines / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids
show 5 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / 4-fluorophenol / 4-halophenol / Aromatic homomonocyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azomethine / Carboximidic acid / Carboximidic acid derivative
show 19 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
112E50TORV
CAS number
62666-20-0
InChI Key
IBALRBWGSVJPAP-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]butanamide
SMILES
NC(=O)CCC\N=C(\C1=CC=C(Cl)C=C1)C1=C(O)C=CC(F)=C1

References

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]
KEGG Drug
D05621
PubChem Compound
5361323
PubChem Substance
46506568
ChemSpider
10642379
RxNav
34568
ChEMBL
CHEMBL287631
ZINC
ZINC000018153101
Therapeutic Targets Database
DAP000258
PharmGKB
PA164747990
Wikipedia
Progabide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)133-135 °CPhysProp
water solubility70.9 mg/LNot Available
logP3.06FARRAJ,NF ET AL. (1988)
Predicted Properties
PropertyValueSource
Water Solubility0.00693 mg/mLALOGPS
logP3.47ALOGPS
logP3.31ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)8.5ChemAxon
pKa (Strongest Basic)4.99ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.68 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity87.95 m3·mol-1ChemAxon
Polarizability33.53 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
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 coup...
Gene Name
GABBR1
Uniprot ID
Q9UBS5
Uniprot Name
Gamma-aminobutyric acid type B receptor subunit 1
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]
Kind
Protein
Organism
Humans
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...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
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]

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

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