- Accession Number
- DB00230 (APRD01198)
- Small Molecule
- Approved, Illicit, Investigational
Pregabalin is an anticonvulsant drug used for neuropathic pain, epilepsy and generalized anxiety disorder. Although as per the FDA Label the mechanism of action has not been definitively defined, there is evidence that pregabalin achieves antihyperalgesic activity by binding to the α2δ subunit of the voltage-dependent calcium channels . Pregabalin is marketed by Pfizer under the trade name Lyrica and Lyrica Cr (extended release).[Label] It may have dependence liability if misused but the risk appears to be highest in patients with current or past substance use disorders .
- (S)-3-Isobutyl GABA
- 3-Isobutyl GABA
- External IDs
- CI 1008 / CI-1008 / PD-144723 / YNP-1807
- Product Images
- Prescription Products
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Ach-pregabalin Capsule 300 mg Oral Accord Healthcare Limited Not applicable Not applicable Ach-pregabalin Capsule 100 mg Oral Accord Healthcare Limited Not applicable Not applicable Ach-pregabalin Capsule 225 mg Oral Accord Healthcare Limited Not applicable Not applicable Ach-pregabalin Capsule 75 mg Oral Accord Healthcare Limited Not applicable Not applicable Ach-pregabalin Capsule 200 mg Oral Accord Healthcare Limited Not applicable Not applicable Ach-pregabalin Capsule 50 mg Oral Accord Healthcare Limited Not applicable Not applicable Ach-pregabalin Capsule 150 mg Oral Accord Healthcare Limited Not applicable Not applicable Ach-pregabalin Capsule 25 mg Oral Accord Healthcare Limited Not applicable Not applicable Apo-pregabalin Capsule 150 mg Oral Apotex Corporation 2013-04-22 Not applicable Apo-pregabalin Capsule 75 mg Oral Apotex Corporation 2013-04-22 Not applicable
- International/Other Brands
- Lyrica (Pfizer) / Lyrica Cr (Pfizer)
- Acids, Acyclic
- Agents causing angioedema
- Agents causing hyperkalemia
- Amino Acids
- Amino Acids, Peptides, and Proteins
- Anti-Anxiety Agents
- Antiarrhythmic agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Cardiovascular Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Fatty Acids
- Fatty Acids, Volatile
- gamma-Aminobutyric Acid
- Hypoglycemia-Associated Agents
- Membrane Transport Modulators
- Miscellaneous Anticonvulsants
- Muscle Relaxants
- Muscle Relaxants, Centrally Acting Agents
- Nervous System
- Peripheral Nervous System Agents
- Potential QTc-Prolonging Agents
- Psychotropic Drugs
- QTc Prolonging Agents
- Sensory System Agents
- Tranquilizing Agents
- Vasodilating Agents
- CAS number
- Average: 159.2261
- Chemical Formula
- InChI Key
- IUPAC Name
- (3S)-3-(aminomethyl)-5-methylhexanoic acid
Pregabalin is used for the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjunctive therapy for adult patients with partial onset seizures [Label].
- Associated Conditions
Pregabalin is structurally analogous to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The molecule acts on voltage gated calcium channels which are widely distributed throughout the central nervous system, allowing it to modulate the release of many excitatory neurotransmitters such as glutamate, substance-P, norepinephrine and calcitonin gene related peptide. This results in inhibition of overexcited neurons, which ultimately returns them to a normal state of function . As a result, Pregabalin has anticonvulsant, analgesic, anxiolytic and sleep modulating effects. 
- Mechanism of action
Pregabalin binds presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system . The mechanism of action has not been fully elucidated but studies suggest that pregabalin produces a disruption of calcium channel trafficking or a reduction of calcium currents. The inhibition of voltage-gated calcium channel subunits reduces calcium release which inhibits the release of several neurotransmitters [Label]. Studies also suggest that the descending noradrenergic and serotonergic pathways originating from the brainstem may be involved with the mechanism of pregabalin. Interestingly, although pregabalin is a structural derivative of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.
Target Actions Organism AVoltage-dependent P/Q-type calcium channel subunit alpha-1Ainhibitor Humans
Pregabalin has linear and dose-proportional absorption with a steady state achieved at 48-72 hours. Currently, there are two different formulations of pregabalin with different pharmacokinetic profiles, one is immediate release while the other is extended release. Pregabalin, in both its forms, presents a rapid absorption at fasting state. Pregabalin has a Cmax of 3.2mcg/ml, Tmax 0.7 hours and AUC 31.5mcg h/ml, while pregabalin CR (extended release) presents a Cmax 2.0mcg/ml, Tmax 8 hours and AUC 29.4mcg h/ml. Pregabalin is absorbed from the small intestine and proximal colon and its AUC values will depend on the type and quantity of meal calories ingested. 
- Volume of distribution
Pregabalin does not bind to plasma proteins . The apparent volume of distribution after oral administration is 0.5 L/kg. It is also likely that pregabalin crosses the blood brain barrier based on evidence from several animal models.
- Protein binding
Pregabalin does not bind to plasma proteins.[Label]
Pregabalin undergoes negligible metabolism in humans.
- Route of elimination
Pregabalin is mainly renally excreted with 98% of the drug eliminated unchanged in the urine, while less than 0.1% of the drug is eliminated through the fecal route. Further, based on preclinical studies, pregabalin does not appear to undergo racemization to the R enantiomer in the body .
- Half life
Mean elimination half-life is 6.3 hours in subjects with normal renal function.
The mean renal clearance is estimated to be 67 to 80.9 ml/min in young healthy subjects. This renal clearance rate along with the drug's lack of plasma protein binding suggests that renal tubular reabsorption is involved.[Label]
The most commonly reported adverse reactions include dizziness, somnolence, blurred vision, dry mouth, weight gain, edema, and changes in concentration and attention [Label].
- Affected organisms
- Humans and other mammals
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction (R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Pregabalin. (S)-Warfarin The metabolism of (S)-Warfarin can be decreased when combined with Pregabalin. 2,4-thiazolidinedione The risk or severity of hypoglycemia can be increased when Pregabalin is combined with 2,4-thiazolidinedione. 3-isobutyl-1-methyl-7H-xanthine Pregabalin may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy. 3,4-Methylenedioxyamphetamine The risk or severity of adverse effects can be increased when Pregabalin is combined with 3,4-Methylenedioxyamphetamine. 3,5-diiodothyropropionic acid The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Pregabalin. 4-Bromo-2,5-dimethoxyamphetamine The risk or severity of adverse effects can be increased when Pregabalin is combined with 4-Bromo-2,5-dimethoxyamphetamine. 4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be decreased when combined with Pregabalin. 4-Methoxyamphetamine The therapeutic efficacy of 4-Methoxyamphetamine can be increased when used in combination with Pregabalin. 5-androstenedione The metabolism of 5-androstenedione can be decreased when combined with Pregabalin.
- Food Interactions
- Avoid alcohol (may increase CNS effects).
- When taken with food, Cmax decreases, while Tmax is prolonged. Despite these observations, the total absorption of pregabalin is not effected to a clinically relevant degree. Pregabalin can be taken with or without food.
- Synthesis Reference
Mark Burk, "Asymmetric synthesis of pregabalin." U.S. Patent US20030212290, issued November 13, 2003.US20030212290
- General References
- Authors unspecified: Schedules of controlled substances: placement of pregabalin into schedule V. Final rule. Fed Regist. 2005 Jul 28;70(144):43633-5. [PubMed:16050051]
- Su TZ, Feng MR, Weber ML: Mediation of highly concentrative uptake of pregabalin by L-type amino acid transport in Chinese hamster ovary and Caco-2 cells. J Pharmacol Exp Ther. 2005 Jun;313(3):1406-15. Epub 2005 Mar 15. [PubMed:15769862]
- Li Z, Taylor CP, Weber M, Piechan J, Prior F, Bian F, Cui M, Hoffman D, Donevan S: Pregabalin is a potent and selective ligand for alpha(2)delta-1 and alpha(2)delta-2 calcium channel subunits. Eur J Pharmacol. 2011 Sep 30;667(1-3):80-90. doi: 10.1016/j.ejphar.2011.05.054. Epub 2011 Jun 1. [PubMed:21651903]
- Bonnet U, Scherbaum N: How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol. 2017 Oct 5. pii: S0924-977X(17)30897-0. doi: 10.1016/j.euroneuro.2017.08.430. [PubMed:28988943]
- Field MJ, Oles RJ, Lewis AS, McCleary S, Hughes J, Singh L: Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents. Br J Pharmacol. 1997 Aug;121(8):1513-22. [PubMed:9283683]
- Rajappa GC, Vig S, Bevanaguddaiah Y, Anadaswamy TC: Efficacy of Pregabalin as Premedication for Post-Operative Analgesia in Vaginal Hysterectomy. Anesth Pain Med. 2016 May 14;6(3):e34591. doi: 10.5812/aapm.34591. eCollection 2016 Jun. [PubMed:27642577]
- Bender G, Florian JA Jr, Bramwell S, Field MJ, Tan KK, Marshall S, DeJongh J, Bies RR, Danhof M: Pharmacokinetic-pharmacodynamic analysis of the static allodynia response to pregabalin and sildenafil in a rat model of neuropathic pain. J Pharmacol Exp Ther. 2010 Aug;334(2):599-608. doi: 10.1124/jpet.110.166074. Epub 2010 May 5. [PubMed:20444880]
- Ben-Menachem E: Pregabalin pharmacology and its relevance to clinical practice. Epilepsia. 2004;45 Suppl 6:13-8. [PubMed:15315511]
- Prompila N, Eiamart W, Jumroen Y, Sayankuldilok N, Chariyavilaskul P, Ketchat W, Wittayalertpanya S: Pharmacokinetics and bioequivalence of a pregabalin 150-mg capsule in healthy Thai subjects. Int J Clin Pharmacol Ther. 2017 Oct;55(10):811-817. doi: 10.5414/CP202954. [PubMed:28513426]
- Hong T, Han S, Lee J, Jeon S, Yim DS: Comparison of oral absorption models for pregabalin: usefulness of transit compartment model. Drug Des Devel Ther. 2016 Dec 7;10:3995-4003. eCollection 2016. [PubMed:27994441]
- Rodriguez J, Castaneda G, Munoz L: Direct determination of pregabalin in human urine by nonaqueous CE-TOF-MS. Electrophoresis. 2013 May;34(9-10):1429-36. doi: 10.1002/elps.201200564. Epub 2013 Apr 16. [PubMed:23463484]
- Randinitis EJ, Posvar EL, Alvey CW, Sedman AJ, Cook JA, Bockbrader HN: Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol. 2003 Mar;43(3):277-83. [PubMed:12638396]
- Gajraj NM: Pregabalin: its pharmacology and use in pain management. Anesth Analg. 2007 Dec;105(6):1805-15. doi: 10.1213/01.ane.0000287643.13410.5e. [PubMed:18042886]
- Pfizer [Link]
- External Links
- ATC Codes
- N03AX16 — Pregabalin
- AHFS Codes
- 28:12.92 — Miscellaneous Anticonvulsants
- FDA label
- Download (3.46 MB)
- Download (106 KB)
- Clinical Trials
- Cp pharmaceuticals cv
- Pfizer inc
- A-S Medication Solutions LLC
- Bryant Ranch Prepack
- Cardinal Health
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Goedecke GmbH
- Innoviant Pharmacy Inc.
- Kaiser Foundation Hospital
- Keltman Pharmaceuticals Inc.
- Lake Erie Medical and Surgical Supply
- Murfreesboro Pharmaceutical Nursing Supply
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- PD-Rx Pharmaceuticals Inc.
- Pfizer Inc.
- Physicians Total Care Inc.
- Prepak Systems Inc.
- Rebel Distributors Corp.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Shasun Chemicals & Drugs Ltd.
- Southwood Pharmaceuticals
- St Mary's Medical Park Pharmacy
- Stat Rx Usa
- US Pharmaceutical Group
- Dosage forms
Form Route Strength Capsule Oral 100 mg/1 Capsule Oral 100 mg Capsule Oral 150 mg/1 Capsule Oral 150 mg Capsule Oral 200 mg/1 Capsule Oral 200 mg Capsule Oral 225 mg Capsule Oral 225 mg/1 Capsule Oral 25 mg Capsule Oral 25 mg/1 Capsule Oral 300 mg Capsule Oral 300 mg/1 Capsule Oral 50 mg/1 Capsule Oral 50 mg Capsule Oral 75 mg Capsule Oral 75 mg/1 Solution Oral 20 mg/1mL Tablet, film coated, extended release Oral 165 mg/1 Tablet, film coated, extended release Oral 330 mg/1 Tablet, film coated, extended release Oral 82.5 mg/1
Unit description Cost Unit Lyrica 100 mg capsule 2.88USD capsule Lyrica 150 mg capsule 2.88USD capsule Lyrica 50 mg capsule 2.88USD capsule Lyrica 75 mg capsule 2.88USD capsule Lyrica 200 mg capsule 2.75USD capsule Lyrica 225 mg capsule 2.75USD capsule Lyrica 25 mg capsule 2.75USD capsule Lyrica 300 mg capsule 2.75USD capsuleDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patent Number Pediatric Extension Approved Expires (estimated) US5563175 No 1996-10-08 2013-10-08 CA2327285 No 2005-06-14 2019-05-10 CA2297163 No 2001-11-20 2018-08-18 US6001876 Yes 1999-12-14 2019-06-30 USRE41920 Yes 2010-11-09 2019-06-30 US6197819 Yes 2001-03-06 2019-06-30 US9144559 Yes 2015-09-29 2027-05-02 US8945620 Yes 2015-02-03 2027-05-02 US10022447 Yes 2007-05-02 2027-05-02
- Experimental Properties
Property Value Source melting point (°C) 186-188ºC Not Available boiling point (°C) 274ºC at 760 mm Hg Not Available water solubility Freely soluble FDA label logP -1.35 FDA label pKa 4.2 and 10.6 FDA label
- Predicted Properties
Property Value Source Water Solubility 11.3 mg/mL ALOGPS logP -1.4 ALOGPS logP -1.3 ChemAxon logS -1.2 ALOGPS pKa (Strongest Acidic) 4.8 ChemAxon pKa (Strongest Basic) 10.23 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 63.32 Å2 ChemAxon Rotatable Bond Count 5 ChemAxon Refractivity 43.68 m3·mol-1 ChemAxon Polarizability 18.08 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon
- Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9727 Blood Brain Barrier + 0.9382 Caco-2 permeable - 0.6531 P-glycoprotein substrate Non-substrate 0.683 P-glycoprotein inhibitor I Non-inhibitor 0.965 P-glycoprotein inhibitor II Non-inhibitor 0.9424 Renal organic cation transporter Non-inhibitor 0.9245 CYP450 2C9 substrate Non-substrate 0.8758 CYP450 2D6 substrate Non-substrate 0.7926 CYP450 3A4 substrate Non-substrate 0.6914 CYP450 1A2 substrate Non-inhibitor 0.9385 CYP450 2C9 inhibitor Non-inhibitor 0.9425 CYP450 2D6 inhibitor Non-inhibitor 0.9539 CYP450 2C19 inhibitor Non-inhibitor 0.9629 CYP450 3A4 inhibitor Non-inhibitor 0.9352 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9784 Ames test Non AMES toxic 0.938 Carcinogenicity Non-carcinogens 0.5678 Biodegradation Ready biodegradable 0.8201 Rat acute toxicity 1.7046 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9868 hERG inhibition (predictor II) Non-inhibitor 0.8909
- Mass Spec (NIST)
- Not Available
- This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
- Organic compounds
- Super Class
- Organic acids and derivatives
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Gamma amino acids and derivatives
- Alternative Parents
- Medium-chain fatty acids / Branched fatty acids / Amino fatty acids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivativesCarbonyl compounds show 1 more
- Gamma amino acid or derivatives / Medium-chain fatty acid / Amino fatty acid / Branched fatty acid / Fatty acyl / Fatty acid / Amino acid / Carboxylic acid / Monocarboxylic acid or derivatives / AminePrimary amine / Organooxygen compound / Organonitrogen compound / Hydrocarbon derivative / Primary aliphatic amine / Organic oxide / Organopnictogen compound / Carbonyl group / Organic oxygen compound / Organic nitrogen compound / Aliphatic acyclic compound show 11 more
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- gamma-amino acid (CHEBI:64356)
- Pharmacological action
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- 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, hor...
- Gene Name
- Uniprot ID
- Uniprot Name
- Voltage-dependent P/Q-type calcium channel subunit alpha-1A
- Molecular Weight
- 282362.39 Da
- 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:17489948]
- 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:16899342]
- Jacquy J, Lossignol D, Sternon J: [Pregabalin (Lyrica) and neuropathic pain syndromes]. Rev Med Brux. 2006 Sep-Oct;27(5):445-50. [PubMed:17144644]
- 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:17126531]
- 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:17088553]
- Pharmacological action
- General Function
- Sodium:dicarboxylate symporter activity
- Specific Function
- Transports L-glutamate, L- and D-aspartate and L-cystein (PubMed:21123949). Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic c...
- Gene Name
- Uniprot ID
- Uniprot Name
- Excitatory amino acid transporter 3
- Molecular Weight
- 57099.835 Da
- Ryu JH, Lee PB, Kim JH, Do SH, Kim CS: Effects of pregabalin on the activity of glutamate transporter type 3. Br J Anaesth. 2012 Aug;109(2):234-9. doi: 10.1093/bja/aes120. Epub 2012 Apr 16. [PubMed:22511482]
Drug created on June 13, 2005 07:24 / Updated on February 18, 2019 20:23