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targets (2)
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Identification
Name Progabide
Accession Number DB00837 (APRD00072)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Halogabide
Progabida [INN-Spanish]
Progabide [Usan:Ban:Inn]
Progabidum [INN-Latin]
Salts Not Available
Brand names
Name Company
Gabren
Gabrene
Brand mixtures Not Available
Categories
  • Antidepressants
  • GABA Agonists
  • Anticonvulsants
  • Antiparkinson Agents
  • Antidyskinetics
  • Antidepressive Agents
CAS number 62666-20-0
Weight Average: 334.773
Monoisotopic: 334.088433678
Chemical Formula C17H16ClFN2O2
InChI Key InChIKey=DWEQWXSKOHHBNT-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+
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropenes
  • Cinnamaldehydes
Substructures
  • Alkanes and Alkenes
  • Amino Ketones
  • Phenylpropenes
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Carbamates and Derivatives
  • Enamines
  • Isoprenes
  • Aromatic compounds
  • Cinnamaldehydes
  • Carboxamides and Derivatives
  • Carboxylic Acids and Derivatives
  • Styrene Derivatives
  • Ketones
Pharmacology
Indication Indicated for the treatment of epilepsy.
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.
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
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
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 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 4.42e-03 g/l ALOGPS
logP 2.68 ALOGPS
logP 1.8 ChemAxon
logS -4.9 ALOGPS
pKa (strongest acidic) 15.32 ChemAxon
pKa (strongest basic) 4.01 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 72.19 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 91.22 ChemAxon
polarizability 33.21 ChemAxon
References
Synthesis Reference Not 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
Resource Link
PubChem Compound 5361323 Link_out
PubChem Substance 46506568 Link_out
ChemSpider 4514729 Link_out
Therapeutic Targets Database DAP000258 Link_out
PharmGKB PA164747990 Link_out
Wikipedia http://en.wikipedia.org/wiki/Progabide Link_out
ATC Codes
  • N03AG05
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Gamma-aminobutyric acid type B receptor, subunit 1

Pharmacological action: yes
Actions: agonist

Isoform 1E function may be to regulate the availability of functional GABA-B-R1A/GABA-B-R2 heterodimers by competing for GABA-B-R2 dimerization. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites

Organism class: human
UniProt ID: Q9UBS5 Link_out
Gene: GABBR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P14867 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19