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
Structure for Progabide (DB00837)
- 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
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- 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.
Target Actions Organism AGamma-aminobutyric acid type B receptor subunit 1 agonistHumans AGamma-aminobutyric acid receptor subunit alpha-1 agonistHumans - 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.
Learn More- 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.
Drug Interaction Unlock Additional DataAcenocoumarol The risk or severity of adverse effects can be increased when Progabide is combined with Acenocoumarol. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Progabide. Acetophenazine The risk or severity of adverse effects can be increased when Progabide is combined with Acetophenazine. Aclidinium Progabide may increase the central nervous system depressant (CNS depressant) activities of Aclidinium. Agomelatine The risk or severity of adverse effects can be increased when Progabide is combined with Agomelatine. Alfentanil The risk or severity of adverse effects can be increased when Alfentanil is combined with Progabide. Alimemazine The risk or severity of adverse effects can be increased when Progabide is combined with Alimemazine. Almotriptan The risk or severity of adverse effects can be increased when Progabide is combined with Almotriptan. Alosetron The risk or severity of adverse effects can be increased when Progabide is combined with Alosetron. Alprazolam The risk or severity of adverse effects can be increased when Alprazolam is combined with Progabide. Additional Data Available- Extended DescriptionExtended DescriptionAvailable for Purchase
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - SeveritySeverityAvailable for Purchase
A severity rating for each drug interaction, from minor to major.
Learn more - Evidence LevelEvidence LevelAvailable for Purchase
A rating for the strength of the evidence supporting each drug interaction.
Learn more - ActionActionAvailable for Purchase
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Not Available
Products
- International/Other Brands
- Gabren / Gabrene (Sanofi S.A.)
Categories
- ATC Codes
- N03AG05 — Progabide
- Drug Categories
- Acids, Acyclic
- Amino Acids
- Amino Acids, Peptides, and Proteins
- Aminobutyrates
- Anti-Dyskinesia Agents
- Anti-Parkinson Drugs
- Anticonvulsants
- Antidepressive Agents
- Butyrates
- Central Nervous System Agents
- Central Nervous System Depressants
- Fatty Acid Derivatives
- Fatty Acids
- Fatty Acids, Volatile
- GABA Agents
- GABA Agonists
- Lipids
- Nervous System
- Neurotransmitter Agents
- Psychotropic Drugs
- 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
- 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
- KEGG Drug
- D05621
- PubChem Compound
- 5361323
- PubChem Substance
- 46506568
- ChemSpider
- 10642379
- 34568
- ChEMBL
- CHEMBL287631
- ZINC
- ZINC000018153101
- Therapeutic Targets Database
- DAP000258
- PharmGKB
- PA164747990
- Wikipedia
- Progabide
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 133-135 °C PhysProp water solubility 70.9 mg/L Not Available logP 3.06 FARRAJ,NF ET AL. (1988) - Predicted Properties
Property Value Source Water Solubility 0.00693 mg/mL ALOGPS logP 3.47 ALOGPS logP 3.31 ChemAxon logS -4.7 ALOGPS pKa (Strongest Acidic) 8.5 ChemAxon pKa (Strongest Basic) 4.99 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 75.68 Å2 ChemAxon Rotatable Bond Count 6 ChemAxon Refractivity 87.95 m3·mol-1 ChemAxon Polarizability 33.53 Å3 ChemAxon Number of Rings 2 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
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 inhibitor Non-inhibitor 0.5455 CYP450 2D6 inhibitor Non-inhibitor 0.7138 CYP450 2C19 inhibitor Inhibitor 0.6943 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available 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
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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- 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]
- 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
- 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]
- 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]
- 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]
- Grech DM, Balster RL: Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats. Psychopharmacology (Berl). 1993;110(3):295-301. [PubMed:7831422]
- 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 December 02, 2020 10:15