PREGABALIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H17NO2
Molecular Weight	159.2261
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](CN)CC(O)=O

InChI

InChIKey=AYXYPKUFHZROOJ-ZETCQYMHSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021446s030,022488s010lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17126531

Pregabalin, marketed under the brand name Lyrica among others. LYRICA is indicated for: Neuropathic pain associated with diabetic peripheral neuropathy (DPN) Postherpetic neuralgia (PHN); Adjunctive therapy for adult patients with partial onset seizures; Fibromyalgia; Neuropathic pain associated with spinal cord injury. It has been shown the clinical effects of pregabalin are likely due to direct and selective interactions with α(2)δ-1 and α(2)δ-2 subunits of voltage-gated calcium channels. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated calcium channel alpha2/delta subunit 2 6 Target ID: CHEMBL3896 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=21651903	Binding Agent 1076
Voltage-gated calcium channel alpha2/delta subunit 1 19 Target ID: CHEMBL1919 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=21651903	Binding Agent 1076

Conditions

Condition	Modality	Highest Phase	Product
Diabetic peripheral neuropathy 8 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021446s030,022488s010lbl.pdf	Palliative	Approved 8583	LYRICA Approved Use LYRICA is indicated for: Management of neuropathic pain associated with diabetic peripheral neuropathy Management of postherpetic neuralgia Adjunctive therapy for adult patients with partial onset seizures Management of fibromyalgia Management of neuropathic pain associated with spinal cord injury LYRICA is indicated for: Neuropathic pain associated with diabetic peripheral neuropathy (DPN) (1) Postherpetic neuralgia (PHN) (1) Adjunctive therapy for adult patients with partial onset seizures (1) Fibromyalgia (1) Neuropathic pain associated with spinal cord injury (1) Launch Date 2004
Postherpetic neuralgia 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021446s030,022488s010lbl.pdf	Palliative	Approved 8583	LYRICA Approved Use LYRICA is indicated for: Management of neuropathic pain associated with diabetic peripheral neuropathy Management of postherpetic neuralgia Adjunctive therapy for adult patients with partial onset seizures Management of fibromyalgia Management of neuropathic pain associated with spinal cord injury LYRICA is indicated for: Neuropathic pain associated with diabetic peripheral neuropathy (DPN) (1) Postherpetic neuralgia (PHN) (1) Adjunctive therapy for adult patients with partial onset seizures (1) Fibromyalgia (1) Neuropathic pain associated with spinal cord injury (1) Launch Date 2004
Partial onset seizures 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021446s030,022488s010lbl.pdf	Palliative	Approved 8583	LYRICA Approved Use LYRICA is indicated for: Management of neuropathic pain associated with diabetic peripheral neuropathy Management of postherpetic neuralgia Adjunctive therapy for adult patients with partial onset seizures Management of fibromyalgia Management of neuropathic pain associated with spinal cord injury LYRICA is indicated for: Neuropathic pain associated with diabetic peripheral neuropathy (DPN) (1) Postherpetic neuralgia (PHN) (1) Adjunctive therapy for adult patients with partial onset seizures (1) Fibromyalgia (1) Neuropathic pain associated with spinal cord injury (1) Launch Date 2004
Fibromyalgia 90 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021446s030,022488s010lbl.pdf	Palliative	Approved 8583	LYRICA Approved Use LYRICA is indicated for: Management of neuropathic pain associated with diabetic peripheral neuropathy Management of postherpetic neuralgia Adjunctive therapy for adult patients with partial onset seizures Management of fibromyalgia Management of neuropathic pain associated with spinal cord injury LYRICA is indicated for: Neuropathic pain associated with diabetic peripheral neuropathy (DPN) (1) Postherpetic neuralgia (PHN) (1) Adjunctive therapy for adult patients with partial onset seizures (1) Fibromyalgia (1) Neuropathic pain associated with spinal cord injury (1) Launch Date 2004

C_max

Value	Dose	Analyte	Population
4155.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3547.82 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3814.52 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
2273.792 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4568.68 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28513426	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
52115.92 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
53348.16 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
47696.84 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
26007.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
29831.454 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28513426	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
6.09 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
6.22 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
6.53 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT
7.78 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34256964/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	PREGABALIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021446s035,022488s013lbl.pdf	unknown, oral	PREGABALIN plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2A6 879 CYP2C19 2057 CYP2E1 1060	P-gp 2052 OCT2 434 OCTN1 55 OAT1 395 OAT3 391 OCTN2 59	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021446s040,%20022488s017lbl.pdf#page=34 Page: 34.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021446s040,%20022488s017lbl.pdf#page=34 Page: 34.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no

Drug as victim

Target	Modality	Activity
OAT1 395	substrate 4014 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=6 Page: 6.0	no
OAT3 391	substrate 4014 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=6 Page: 6.0	no
OCTN2 59	substrate 4014 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=6 Page: 6.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=25 Page: 25.0	no
OCT2 434	substrate 4014 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=5 Page: 5.0	yes
OCTN1 55	substrate 4014 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=5 Page: 5.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ema.europa.eu/en/documents/scientific-discussion-variation/lyrica-h-c-546-ii-0004-epar-scientific-discussion-variation_en.pdf#page=2 Page: 2.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:64356	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:64356
ChemicalBook	CB2251105	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2251105
eMolecules	8324194	https://www.emolecules.com/cgi-bin/more?vid=8324194
ZINC	ZINC000000005152	http://zinc15.docking.org/substances/ZINC000000005152

PubMed

Title	Date	PubMed
Pregabalin: in the treatment of postherpetic neuralgia.	2005	15610058
Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial.	2004-12-14	15596757
Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).	2004-12-02	15570674
Gateways to clinical trials.	2004-11	15632957
Simultaneous high-performance liquid chromatographic analysis of pregabalin, gabapentin and vigabatrin in human serum by precolumn derivatization with o-phtaldialdehyde and fluorescence detection.	2004-10-25	15380728
Gateways to clinical trials.	2004-10	15605126
Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines.	2004-10	15380158
'Protective premedication': an option with gabapentin and related drugs? A review of gabapentin and pregabalin in in the treatment of post-operative pain.	2004-10	15352959
Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology.	2004-09-28	15452284
Gateways to clinical trials.	2004-09-07	15349141
Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro.	2004-09	15355323
A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats.	2004-08-04	15294026
Mechanism of action of alpha2delta ligands: voltage sensitive calcium channel (VSCC) modulators.	2004-08	15323585
Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial.	2004-08	15288403
Pharmaceutical treatment options for fibromyalgia.	2004-08	15251075
Neuromodulating drugs for the symptomatic treatment of neuropathic pain.	2004-06	15115640
[New options in the treatment of various forms of diabetic neuropathy].	2004-05-20	15373085
Highly selective asymmetric hydrogenation using a three hindered quadrant bisphosphine rhodium catalyst.	2004-05-19	15137752
Effect of gabapentin derivates on mechanical allodynia-like behaviour in a rat model of chronic sciatic constriction injury.	2004-05-17	15109646
Anticonvulsants and the relief of chronic pain: pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels.	2004-05	15163243
American Chemical Society--227th annual meeting. Neuroprotection. 28 March - 1 April 2004, Anaheim, CA, USA.	2004-05	15154101
Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial.	2004-05	15082123
[How neuropathic is sciatica? The mixed pain concept].	2004-05	15067505
Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study.	2004-04	15206660
Gateways to clinical trials.	2004-04	15148527
Anticonvulsants as anxiolytics, part 2: Pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels.	2004-04	15119905
Gateways to clinical trials.	2004-03	15071612
Pharmacologic management part 1: better-studied neuropathic pain diseases.	2004-03	14996228
Gateways to clinical trials.	2004-02-28	14988742
High dose pregabalin is effective for the treatment of generalised anxiety disorder.	2004-02	14769661
Pregabalin (Pfizer).	2004-01	14983979
Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures.	2004-01	14692903
Pregabalin: in the treatment of painful diabetic peripheral neuropathy.	2004	15563250
[New molecular targets in pharmacological treatment of anxiety disorders].	2004	15505688
Antiepileptic drugs in the treatment of anxiety disorders: role in therapy.	2004	15456335
Selecting pharmacotherapy for generalized anxiety disorder.	2004	15384931
The biology and pharmacology of calcium channel alpha2-delta proteins Pfizer Satellite Symposium to the 2003 Society for Neuroscience Meeting. Sheraton New Orleans Hotel, New Orleans, LA November 10, 2003.	2004	15317151
Pregabalin as adjunctive therapy for partial seizures.	2004	15315512
Pregabalin pharmacology and its relevance to clinical practice.	2004	15315511
Newer anticonvulsants in the treatment of bipolar disorder.	2004	15242330
Gateways to clinical trials.	2003-12	14735233
Genotype-dependence of gabapentin and pregabalin sensitivity: the pharmacogenetic mediation of analgesia is specific to the type of pain being inhibited.	2003-12	14659515
Future Pain Drugs - Europe 2003. 15-16 September 2003, London, UK.	2003-11	15270029
The use of clinical trial simulation to support dose selection: application to development of a new treatment for chronic neuropathic pain.	2003-11	14661918
Gateways to clinical trials.	2003-10	14671684
Gateways to clinical trials.	2003-09	14571286
Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C.	2003-09	14499429
Evaluation of mixture modeling with count data using NONMEM.	2003-06	14571690
The role of GABA in the pathophysiology and treatment of anxiety disorders.	2003	15131523
New single-isomer compounds on the horizon.	2002-04	15131493

Patents

Sample Use Guides

In Vivo Use Guide

Neuropathic Pain Associated with Diabetic Peripheral Neuropathy: The maximum recommended dose is 100 mg three times a day (300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Postherpetic Neuralgia: The recommended dose is 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 75 mg two times a day, or 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability. Adjunctive Therapy for Adult Patients with Partial Onset Seizures: LYRICA at doses of 150 to 600 mg/day has been shown to be effective as adjunctive therapy in the treatment of partial onset seizures in adults. Both the efficacy and adverse event profiles of In general, it is recommended that patients be started on a total daily dose no greater than 150 mg/day (75 mg two times a day, or 50 mg three times a day). Management of Fibromyalgia: The recommended dose is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Neuropathic Pain Associated with Spinal Cord Injury: The recommended dose range is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

VRONOGABIC

Preferred Name

English

PREGABALIN

Official Name

English

NSC-759256

Code

English

PREGABALIN [ORANGE BOOK]

Common Name

English

(S)-3-(AMINOMETHYL)-5-METHYLHEXANOIC ACID

Systematic Name

English

PREGABALIN [USAN]

Common Name

English

PREGABALIN [VANDF]

Common Name

English

PREGABALIN [JAN]

Common Name

English

PREGABALIN SANDOZ

Brand Name

English

LYRICA CR

Brand Name

English

PREGABALIN [MART.]

Common Name

English

PREGABALIN MYLAN

Brand Name

English

pregabalin [INN]

Common Name

English

CI-1008

Code

English

Pregabalin [WHO-DD]

Common Name

English

PREGABALIN [HSDB]

Common Name

English

PREGABALIN ZENTIVA

Brand Name

English

LYRICA

Brand Name

English

PREGABALIN [MI]

Common Name

English

PREGABALIN MYLAN PHARMA

Brand Name

English

PD-144723

Code

English

PREGABALIN [USP-RS]

Common Name

English

PREGABALIN SANDOZ GMBH

Brand Name

English

PREGABALIN [USP MONOGRAPH]

Common Name

English

YNP-1807

Code

English

PREGABALIN [EP MONOGRAPH]

Common Name

English

PREGABALIN [EMA EPAR]

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

PREGABALIN PFIZER (AUTHORIZED: NEURALGIA)