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Identification
Name Pregabalin
Accession Number DB00230 (APRD01198)
Type small molecule
Groups illicit, approved
Description

Pregabalin is an anticonvulsant drug used for neuropathic pain, as an adjunct therapy for partial seizures, and in generalized anxiety disorder. It was designed as a more potent successor to gabapentin. Pregabalin is marketed by Pfizer under the trade name Lyrica. It is considered to have a dependence liability if misused, and is classified as a Schedule V drug in the U.S. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • pregabalin
Brand names
  • Lyrica
Brand name mixtures Not Available
Categories
  • Anticonvulsants
  • Analgesics
CAS number 148553-50-8
Weight Average: 159.2261
Monoisotopic: 159.125928793
Chemical Formula C8H17NO2
InChI Key InChIKey=AYXYPKUFHZROOJ-ZETCQYMHSA-N
InChI
InChI=1S/C8H17NO2/c1-6(2)3-7(5-9)4-8(10)11/h6-7H,3-5,9H2,1-2H3,(H,10,11)/t7-/m0/s1
Plain Text
IUPAC Name
(3S)-3-(aminomethyl)-5-methylhexanoic acid
SMILES
CC(C)C[C@H](CN)CC(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
  • Carboxylic Acids and Derivatives
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
Pharmacology
Indication For management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia.
Pharmacodynamics Pregabalin is a new anticonvulsant drug indicated as an add on therapy for partial onset seizures and for certain types of neuropathic pain. It was designed as a more potent successor to a related drug, gabapentin. Pregabalin binds to the alpha2-delta subunit of the voltage-gated calcium channel in the central nervous system. While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Mechanism of action Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalinís antinociceptive and antiseizure effects in animal models. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.
Absorption Well absorbed after oral administration.
Volume of distribution
  • 0.5 L/kg
Protein binding Not Available
Metabolism

Negligible
Route of elimination Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug.
Half life ~6 hours
Clearance
  • Renal cl=67.0 – 80.9 mL/min [young healthy subjects]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Cp pharmaceuticals cv
  • Pfizer inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Lyrica 100 mg capsule 2.88 USD capsule
Lyrica 150 mg capsule 2.88 USD capsule
Lyrica 50 mg capsule 2.88 USD capsule
Lyrica 75 mg capsule 2.88 USD capsule
Lyrica 200 mg capsule 2.75 USD capsule
Lyrica 225 mg capsule 2.75 USD capsule
Lyrica 25 mg capsule 2.75 USD capsule
Lyrica 300 mg capsule 2.75 USD capsule
Patents
Country Patent Number Approved Expires
United States 6001876 1998-12-30 2018-12-30
United States 5563175 1993-10-08 2013-10-08
Canada 2327285 2005-06-14 2019-05-10
Canada 2297163 2001-11-20 2018-08-18
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 1.3 PhysProp
Predicted Properties
Property Value Source
water solubility 1.13e+01 g/l ALOGPS
logP -1.35 ALOGPS
logP -1.58 ChemAxon Molconvert
logS -1.15 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 63.32 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 43.68 ChemAxon Molconvert
polarizability 18.08 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. : Schedules of controlled substances: placement of pregabalin into schedule V. Final rule. Fed Regist. 2005 Jul 28;70(144):43633-5. Pubmed
External Links
Resource Link
KEGG Drug D02716 Link_out
PubChem Compound 5486971 Link_out
PubChem Substance 46504934 Link_out
ChemSpider 4589156 Link_out
BindingDB 50164279 Link_out
Therapeutic Targets Database DAP001264 Link_out
Drug Product Database 2268418 Link_out
RxList http://www.rxlist.com/cgi/generic/lyrica.htm Link_out
Drugs.com http://www.drugs.com/cdi/pregabalin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Pregabalin Link_out
ATC Codes
  • N03AX16
AHFS Codes
  • 28:12.92
PDB Entries Not Available
FDA label show (3.5 MB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol (may increase CNS effects).
  • Take without regard to meals.
Targets

1. Voltage-dependent P/Q-type calcium channel subunit alpha-1A

Pharmacological action: yes
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the "high-voltage activated" (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin- IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA)

Organism class: human
UniProt ID: O00555 Link_out
Gene: CACNA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gazulla J, Tintore M: The P/Q-type voltage-dependent calcium channel: a therapeutic target in spinocerebellar ataxia type 6. Acta Neurol Scand. 2007 May;115(5):356-63. Pubmed
  2. Gazulla J, Tintore MA: The P/Q-type voltage-dependent calcium channel as pharmacological target in spinocerebellar ataxia type 6: gabapentin and pregabalin may be of therapeutic benefit. Med Hypotheses. 2007;68(1):131-6. Epub 2006 Aug 8. Pubmed
  3. Jacquy J, Lossignol D, Sternon J: [Pregabalin (Lyrica) and neuropathic pain syndromes] Rev Med Brux. 2006 Sep-Oct;27(5):445-50. Pubmed
  4. Taylor CP, Angelotti T, Fauman E: Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007 Feb;73(2):137-50. Epub 2006 Nov 28. Pubmed
  5. Field MJ, Cox PJ, Stott E, Melrose H, Offord J, Su TZ, Bramwell S, Corradini L, England S, Winks J, Kinloch RA, Hendrich J, Dolphin AC, Webb T, Williams D: Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17537-42. Epub 2006 Nov 6. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:37

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.