PREGABALIN ARENACARBIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H27NO6
Molecular Weight	317.378
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](CNC(=O)O[C@H](C)OC(=O)C(C)C)CC(O)=O

InChI

InChIKey=YDHZNJWFIYERIF-NEPJUHHUSA-N

InChI=1S/C15H27NO6/c1-9(2)6-12(7-13(17)18)8-16-15(20)22-11(5)21-14(19)10(3)4/h9-12H,6-8H2,1-5H3,(H,16,20)(H,17,18)/t11-,12+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C15H27NO6
Molecular Weight	317.378
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
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
New single-isomer compounds on the horizon.	2002 Apr	15131493
The role of GABA in the pathophysiology and treatment of anxiety disorders.	2003	15131523
Gateways to clinical trials.	2003 Dec	14735233
Genotype-dependence of gabapentin and pregabalin sensitivity: the pharmacogenetic mediation of analgesia is specific to the type of pain being inhibited.	2003 Dec	14659515
Evaluation of mixture modeling with count data using NONMEM.	2003 Jun	14571690
Future Pain Drugs - Europe 2003. 15-16 September 2003, London, UK.	2003 Nov	15270029
The use of clinical trial simulation to support dose selection: application to development of a new treatment for chronic neuropathic pain.	2003 Nov	14661918
Gateways to clinical trials.	2003 Oct	14671684
Gateways to clinical trials.	2003 Sep	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 Sep	14499429
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
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
Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study.	2004 Apr	15206660
Gateways to clinical trials.	2004 Apr	15148527
Anticonvulsants as anxiolytics, part 2: Pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels.	2004 Apr	15119905
Mechanism of action of alpha2delta ligands: voltage sensitive calcium channel (VSCC) modulators.	2004 Aug	15323585
Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial.	2004 Aug	15288403
Pharmaceutical treatment options for fibromyalgia.	2004 Aug	15251075
A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats.	2004 Aug 4	15294026
Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial.	2004 Dec 14	15596757
High dose pregabalin is effective for the treatment of generalised anxiety disorder.	2004 Feb	14769661
Pregabalin (Pfizer).	2004 Jan	14983979
Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures.	2004 Jan	14692903
Gateways to clinical trials.	2004 Jan-Feb	14988742
Gateways to clinical trials.	2004 Jul-Aug	15349141
Neuromodulating drugs for the symptomatic treatment of neuropathic pain.	2004 Jun	15115640
Gateways to clinical trials.	2004 Mar	15071612
Pharmacologic management part 1: better-studied neuropathic pain diseases.	2004 Mar	14996228
Anticonvulsants and the relief of chronic pain: pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels.	2004 May	15163243
American Chemical Society--227th annual meeting. Neuroprotection. 28 March - 1 April 2004, Anaheim, CA, USA.	2004 May	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 May	15082123
[How neuropathic is sciatica? The mixed pain concept].	2004 May	15067505
Effect of gabapentin derivates on mechanical allodynia-like behaviour in a rat model of chronic sciatic constriction injury.	2004 May 17	15109646
Highly selective asymmetric hydrogenation using a three hindered quadrant bisphosphine rhodium catalyst.	2004 May 19	15137752
[New options in the treatment of various forms of diabetic neuropathy].	2004 May 20	15373085
Gateways to clinical trials.	2004 Nov	15632957
Gateways to clinical trials.	2004 Oct	15605126
Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines.	2004 Oct	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 Oct	15352959
Simultaneous high-performance liquid chromatographic analysis of pregabalin, gabapentin and vigabatrin in human serum by precolumn derivatization with o-phtaldialdehyde and fluorescence detection.	2004 Oct 25	15380728
Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro.	2004 Sep	15355323
Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology.	2004 Sep 28	15452284
Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).	2004 Sep-Oct	15570674
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 Summer	15317151
Pregabalin: in the treatment of postherpetic neuralgia.	2005	15610058

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 `Sat Dec 16 10:08:33 GMT 2023` Edited by `admin` on `Sat Dec 16 10:08:33 GMT 2023`
Record UNII	JNY093NZ79
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PREGABALIN ARENACARBIL

Official Name

English

pregabalin arenacarbil [INN]

Common Name

English

HEXANOIC ACID, 5-METHYL-3-(((((1R)-1-(2-METHYL-1-OXOPROPOXY)ETHOXY)CARBONYL)AMINO)METHYL)-, (3S)-

Systematic Name

English

(3S)-5-METHYL-3-(((((1R)-1-(2-METHYL-1-OXOPROPOXY)ETHOXY)CARBONYL)AMINO)METHYL)HEXANOIC ACID

Systematic Name

English

Code System Code Type Description

FDA UNII

JNY093NZ79