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

Molecular Formula	C8H17NO2
Molecular Weight	159.2261
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 1064
Voltage-gated calcium channel alpha2/delta subunit 1 19 Target ID: CHEMBL1919 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=21651903	Binding Agent 1064

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 8429	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 8429	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 8429	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 89 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021446s030,022488s010lbl.pdf	Palliative	Approved 8429	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	Co-administered	Analyte	Population
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	Co-administered	Analyte	Population
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	Co-administered	Analyte	Population
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

Doses

Dose	Population	Adverse events
600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/30349198	healthy, 24.8 years n = 10 Health Status: healthy Age Group: 24.8 years Sex: M Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/30349198	Other AEs: Vision blurred, Nausea... Other AEs: Vision blurred (moderate, 1 patient) Nausea (moderate, 1 patient) Dizziness (mild, 4 patients) Dysarthria (moderate, 1 patient) Headache (mild, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/30349198
600 mg 1 times / day multiple, oral Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17580330	unhealthy, 53.91 years n = 22 Health Status: unhealthy Condition: Essential Tremor Age Group: 53.91 years Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/17580330	Sources: https://pubmed.ncbi.nlm.nih.gov/17580330
150 mg 1 times / day steady, oral Dose: 150 mg, 1 times / day Route: oral Route: steady Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021446s040,%20022488s017lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_medr.PDF	unhealthy, adult n = 979 Health Status: unhealthy Age Group: adult Population Size: 979 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021446s040,%20022488s017lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_medr.PDF	Disc. AE: Dizziness, Somnolence... AEs leading to discontinuation/dose reduction: Dizziness (3.47%) Somnolence (2.76%) Asthenia (0.82%) Confusion (0.72%) Peripheral edema (0.61%) Headache (1.12%) Amblyopia (0.82%) Dry mouth (0.72%) Nausea (0.72%) Infection (0.41%) Ataxia (0.41%) Neuropathy (0.41%) Tremor (0.41%) Constipation (0.31%) Diarrhea (0.31%) Incoordination (0.31%) Abnormal thinking (0.31%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021446s040,%20022488s017lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_medr.PDF

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882	P-gp 1537 OCT2 355 OCTN1 47 OAT1 326 OAT3 339 OCTN2 50	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021446s040,%20022488s017lbl.pdf#page=34 Page: 34.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=5 Page: 5.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021446s040,%20022488s017lbl.pdf#page=34 Page: 34.0	no
CYP3A4 1925	inhibitor 3277 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 326	substrate 3367 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=6 Page: 6.0	no
OAT3 339	substrate 3367 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=6 Page: 6.0	no
OCTN2 50	substrate 3367 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=6 Page: 6.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021446_Lyrica%20Capsules_biopharmr.PDF#page=25 Page: 25.0	no
OCT2 355	substrate 3367 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=5 Page: 5.0	yes
OCTN1 47	substrate 3367 Sources: https://www.iqpc.com/media/8156/15859.pdf#page=5 Page: 5.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
ZINC	ZINC000000005152	http://zinc15.docking.org/substances/ZINC000000005152
eMolecules	8324194	https://www.emolecules.com/cgi-bin/more?vid=8324194

PubMed

Title	Date	PubMed
Future prospects for the drug treatment of epilepsy.	2001	11735615
The new generation of GABA enhancers. Potential in the treatment of epilepsy.	2001	11475940
Stereospecific effect of pregabalin on ectopic afferent discharges and neuropathic pain induced by sciatic nerve ligation in rats.	2001 Dec	11748408
Pharmacotherapy of social anxiety disorder at the turn of the millennium.	2001 Dec	11723633
Pregabalin enhances nonrapid eye movement sleep.	2001 Dec	11714899
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V).	2001 Jan	11137386
Vincristine-induced allodynia in the rat.	2001 Jul	11406340
Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.	2001 Nov	11690728
Gateways to clinical trials.	2002 Dec	12616965
Inhibition of neuronal Ca(2+) influx by gabapentin and pregabalin in the human neocortex.	2002 Feb	11804619
Gateways to Clinical Trials. June 2002.	2002 Jun	12168506
Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia.	2002 Nov	12411814
The role of GABA in the pathophysiology and treatment of anxiety disorders.	2003	15131523
Patient pages. Treatment of postherpetic neuralgia.	2003 Apr 22	12707463
Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial.	2003 Apr 22	12707429
Synthesis of both enantiomers of a P-chirogenic 1,2-bisphospholanoethane ligand via convergent routes and application to rhodium-catalyzed asymmetric hydrogenation of CI-1008 (pregabalin).	2003 Aug 27	12926944
Genotype-dependence of gabapentin and pregabalin sensitivity: the pharmacogenetic mediation of analgesia is specific to the type of pain being inhibited.	2003 Dec	14659515
Gateways to clinical trials.	2003 Jan-Feb	12690708
Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations.	2003 Jul	12810343
An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation.	2003 Jul 11	12839471
Evaluation of mixture modeling with count data using NONMEM.	2003 Jun	14571690
Gateways to clinical trials.	2003 Jun	12851663
Exposure-response analysis of pregabalin add-on treatment of patients with refractory partial seizures.	2003 Jun	12811359
Gateways to clinical trials. March 2003.	2003 Mar	12731460
Pharmacokinetics of pregabalin in subjects with various degrees of renal function.	2003 Mar	12638396
Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures.	2003 May 27	12771254
[New molecular targets in pharmacological treatment of anxiety disorders].	2004	15505688
Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study.	2004 Apr	15206660
Anticonvulsants as anxiolytics, part 2: Pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels.	2004 Apr	15119905
Gateways to clinical trials.	2004 Jan-Feb	14988742
Neuromodulating drugs for the symptomatic treatment of neuropathic pain.	2004 Jun	15115640
American Chemical Society--227th annual meeting. Neuroprotection. 28 March - 1 April 2004, Anaheim, CA, USA.	2004 May	15154101
Gateways to clinical trials.	2004 Nov	15632957
Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro.	2004 Sep	15355323
Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).	2004 Sep-Oct	15570674

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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:45:33 GMT 2023` Edited by `admin` on `Fri Dec 15 15:45:33 GMT 2023`
Record UNII	55JG375S6M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

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

VRONOGABIC

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)