Progabide
Identification
- Generic Name
- Progabide
- DrugBank Accession Number
- DB00837
- Background
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
- 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.
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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.
Target Actions Organism AGamma-aminobutyric acid receptor subunit alpha-1 agonistHumans AGamma-aminobutyric acid type B receptor subunit 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- 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 software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Progabide is combined with 1,2-Benzodiazepine. Acenocoumarol The risk or severity of adverse effects can be increased when Progabide is combined with Acenocoumarol. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Progabide. Acetophenazine The risk or severity of CNS depression can be increased when Progabide is combined with Acetophenazine. Agomelatine The risk or severity of CNS depression can be increased when Progabide is combined with Agomelatine. - Food Interactions
- Not Available
Products
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- 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
- GABA Agents
- GABA Agonists
- Nervous System
- Neurotransmitter Agents
- Psychotropic Drugs
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 38C836J57Z
- CAS number
- 62666-20-0
- InChI Key
- IBALRBWGSVJPAP-UHFFFAOYSA-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)
- IUPAC Name
- 4-{[(4-chlorophenyl)(5-fluoro-2-hydroxyphenyl)methylidene]amino}butanimidic acid
- SMILES
- OC(=N)CCCN=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. [Article]
- External Links
- KEGG Drug
- D05621
- PubChem Compound
- 5361323
- PubChem Substance
- 46506568
- ChemSpider
- 21161991
- 34568
- ChEBI
- 135422
- 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 logP 1.47 Chemaxon pKa (Strongest Acidic) -1.1 Chemaxon pKa (Strongest Basic) 12 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 76.67 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 98.89 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 MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014r-0009000000-8674277cea362227ad50 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00kb-0097000000-1d46130092f5ef440038 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00kr-0094000000-082ff16fc760e1babca8 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000m-8973000000-ea5bceaf7562f7c12818 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0019-0590000000-8dc41c86544a13f4e863 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001u-9431000000-49c14986d651076b5f4a Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Grech DM, Balster RL: Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats. Psychopharmacology (Berl). 1993;110(3):295-301. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:45