PERHEXILINE MALEATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H35N.C4H4O4
Molecular Weight	393.5601
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.C(C(C1CCCCC1)C2CCCCC2)C3CCCCN3

InChI

InChIKey=JDZOTSLZMQDFLG-BTJKTKAUSA-N

InChI=1S/C19H35N.C4H4O4/c1-3-9-16(10-4-1)19(17-11-5-2-6-12-17)15-18-13-7-8-14-20-18;5-3(6)1-2-4(7)8/h16-20H,1-15H2;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula	C19H35N
Molecular Weight	277.4879
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17445089 | http://www.medsafe.govt.nz/profs/Datasheet/p/pexsigtab.pdf | http://adisinsight.springer.com/drugs/800037277

Perhexiline, 2-(2,2-dicyclohexylethyl)piperidine, is an anti-anginal drug. Perhexiline reduces fatty acid metabolism through the inhibition of carnitine palmitoyltransferase, the enzyme responsible for mitochondrial uptake of long-chain fatty acids. Perhexiline is used for reducing the frequency of moderate to severe attacks of angina pectoris due to coronary artery disease in patients who have not responded to other conventional therapy or in whom such therapy may be contraindicated. Heart Metabolics Limited is developing perhexiline for the treatment of hypertrophic cardiomyopathy

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Carnitine palmitoyltransferase 1A 5 Target ID: CHEMBL3858 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8694852	Inhibitor 8504	77.0 µM [IC50]
Carnitine palmitoyltransferase 1B 5 Target ID: CHEMBL3216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8694852	Inhibitor 8504	148.0 µM [IC50]
HERG 99 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10369479 \| https://www.ncbi.nlm.nih.gov/pubmed/18701618	Blocker 555	7.8 µM [IC50]
Voltage-gated potassium channel subunit Kv1.5 43 Target ID: CHEMBL4306 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7616429	Blocker 555	1.5 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Angina pectoris 110 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17445089	Primary	Approved 8583	PEXSIG Approved Use To reduce the frequency of moderate to severe attacks of angina pectoris due to coronary artery disease in patients who have not responded to other conventional therapy or in whom such therapy may be contraindicated. Launch Date 1977
Hypertrophic cardiomyopathy 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20921436	Primary	Phase II 1147	Unknown Approved Use Unknown
Schistosomiasis 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27518281	Primary	Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
66.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7264901/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		PERHEXILINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
274 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7264901/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		PERHEXILINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1010 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7264901/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		PERHEXILINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
5110 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7264901/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		PERHEXILINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7264901/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		PERHEXILINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
19.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7264901/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		PERHEXILINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2.4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27518281/			PERHEXILINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
6500 mg single, oral Accidental dose Dose: 6500 mg Route: oral Route: single Dose: 6500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15228400/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15228400/	Other AEs: Nausea, Vomiting... Other AEs: Nausea Vomiting Sources: https://pubmed.ncbi.nlm.nih.gov/15228400/
100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6263960/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6263960/	Disc. AE: Parkinsonism, Peripheral neuropathy... AEs leading to discontinuation/dose reduction: Parkinsonism (grade 1) Peripheral neuropathy Sources: https://pubmed.ncbi.nlm.nih.gov/6263960/
300 mg 3 times / day multiple, oral Studied dose Dose: 300 mg, 3 times / day Route: oral Route: multiple Dose: 300 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6572824/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6572824/	Other AEs: Cirrhosis liver... Other AEs: Cirrhosis liver (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/6572824/

AEs

AE	Significance	Dose	Population
Nausea		6500 mg single, oral Accidental dose Dose: 6500 mg Route: oral Route: single Dose: 6500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15228400/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15228400/
Vomiting		6500 mg single, oral Accidental dose Dose: 6500 mg Route: oral Route: single Dose: 6500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15228400/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/15228400/
Peripheral neuropathy	Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6263960/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6263960/
Parkinsonism	grade 1 Disc. AE	100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6263960/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6263960/
Cirrhosis liver	grade 5	300 mg 3 times / day multiple, oral Studied dose Dose: 300 mg, 3 times / day Route: oral Route: multiple Dose: 300 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6572824/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6572824/

PubMed

Title	Date	PubMed
A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis.	2013-02	23243064
Comparison of a genomic and a multiplex cell imaging approach for the detection of phospholipidosis.	2011-10	21515356
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011-07-14	21599003
Niclosamide prevents the formation of large ubiquitin-containing aggregates caused by proteasome inhibition.	2010-12-23	21203451
Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure.	2010-11-16	21080957
Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy.	2010-10-19	20921440
Perhexiline and hypertrophic cardiomyopathy: a new horizon for metabolic modulation.	2010-10-19	20921436
A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs.	2010-08	21304177
Modulation of myocardial metabolism: an emerging therapeutic principle.	2010-07	20535068
Metabolic Fingerprinting in Toxicological Assessment Using FT-ICR MS.	2010-06	22272014
Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases.	2010-04-09	20147746
Effects of perhexiline on myocardial deformation in patients with ischaemic left ventricular dysfunction.	2010-03-04	19840889
Lack of effect of perhexiline in ischaemic heart failure.	2010-03-04	19748138
The pathophysiology of diastolic heart failure.	2010-02-24	20948816
Stereoselective Inhibition of the hERG1 Potassium Channel.	2010	21833176
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.	2009-12-02	19956587
Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond.	2009-12	19876734
The adrenergic-fatty acid load in heart failure.	2009-10-27	19850204
Determination of perhexiline and its metabolite hydroxyperhexiline in human plasma by liquid chromatography/tandem mass spectrometry.	2009-10-01	19646935
Relationship between in vitro phospholipidosis assay using HepG2 cells and 2-week toxicity studies in rats.	2009-10	19793005
Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling.	2009-09-22	19771169
Multi-centre experience on the use of perhexiline in chronic heart failure and refractory angina: old drug, new hope.	2009-09	19656806
Multiplexed assay panel of cytotoxicity in HK-2 cells for detection of renal proximal tubule injury potential of compounds.	2009-09	19523510
Diabetic cardiomyopathy.	2009-05	19364331
Effect of intracellular lipid droplets on cytosolic Ca2+ and cell death during ischaemia-reperfusion injury in cardiomyocytes.	2009-03-15	19188253
Overview of therapeutic drug monitoring.	2009-03	19270474
Ca2+-dependent functions in peptidoglycan-stimulated mouse dendritic cells.	2009	19710531
Effects of metabolic approach in diabetic patients with coronary artery disease.	2009	19275650
The metabolic treatment of coronary artery disease and heart failure.	2009	19275645
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.	2008-12	18493746
Drug binding to the inactivated state is necessary but not sufficient for high-affinity binding to human ether-à-go-go-related gene channels.	2008-11	18701618
Chronic stable angina pectoris.	2008-09	18725007
Steatohepatitis-inducing drugs trigger cytokeratin cross-links in hepatocytes. Possible contribution to Mallory-Denk body formation.	2008-09	18603402
Metabolic agents in the management of diabetic coronary patients: a new era.	2008-06-23	18199501
Metabolic agents in the management of diabetic coronary patients: a new era.	2008-06-23	17561287
Gene expression profiling in rat liver treated with compounds inducing phospholipidosis.	2008-06-15	18355885
Phospholipidosis assay in HepG2 cells and rat or rhesus hepatocytes using phospholipid probe NBD-PE.	2008-06	18537465
The pathophysiology of heart failure: a tale of two old paradigms revisited.	2008-04	18478870
Steady-state pharmacokinetics of the enantiomers of perhexiline in CYP2D6 poor and extensive metabolizers administered Rac-perhexiline.	2008-03	17875193
Management of the metabolic syndrome in cardiovascular disease.	2008-02	18325305
Overview of emerging pharmacologic agents for acute heart failure syndromes.	2008-02	18279775
Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.	2008-02	18224312
Metabolic therapy of heart failure.	2008	18991675
Modulation of cardiac metabolism during myocardial ischemia.	2008	18991673
Impaired tissue responsiveness to organic nitrates and nitric oxide: a new therapeutic frontier?	2007-11	17765975
In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies.	2007-09	17567588
Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.	1985-09-01	4029887
Perhexilene neuropathy: a report of two cases.	1984-06	6093756
[The classic anti-anginal agents and molsidomine].	1983-02	6407452
[Electrophysiological study of latent neuropathies induced by perhexiline].	1978-11	81769

Patents

Sample Use Guides

In Vivo Use Guide

Commence therapy with 100mg daily. Adjust progressively, up or down, at 2 to 4 weekly intervals based on the results of plasma level monitoring. It is generally advised not to administer more than 300mg per day, in divided doses, but in certain cases it may be necessary to use 400mg per day. The maintenance dose must be the minimum dose that is effective and well tolerated.

Route of Administration: Oral

In Vitro Use Guide

Perhexiline maleate was more potent on basal LH release from rat anterior pituitary cell aggregates than on LH stimulated by LHRH. The increases of basal LH secretion induced by perhexiline maleate were 69% (p < 0.001) at a concentration of 10(-7)M, 130% (p < 0.001) at a concentration of 10(-5)M and 250% (p < 0.001) at a concentration of 10(-4)M. Perhexiline maleate also increased the LHRH-stimulated LH release by 25.5% (p < 0.05) at a concentration of 10(-5)M and by 74.5% (p < 0.01) at the concentration of 10(-4)M.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:57:55 GMT 2025` Edited by `admin` on `Mon Mar 31 17:57:55 GMT 2025`
Record UNII	K7V8Y90G0H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PERHEXILINUM

Preferred Name

English

PERHEXILINE MALEATE

Official Name

English

2-(2,2-DICYCLOHEXYLETHYL)PIPERIDINE MALEATE

Systematic Name

English

PIPERIDINE, 2-(2,2-DICYCLOHEXYLETHYL)-, MALEATE

Systematic Name

English

Perhexiline maleate [WHO-DD]

Common Name

English

PERHEXILINUM [HPUS]

Common Name

English

PERHEXILINE MALEATE [MI]

Common Name

English

NSC-758409

Code

English

PIPERIDINE, 2-(2,2-DICYCLOHEXYLETHYL)-, MALEATE (1:1)

Systematic Name

English

PERHEXILINE MALEATE [USAN]

Common Name

English

PERHEXILINE MALEATE [MART.]

Common Name

English

PIPERIDINE, 2-(2,2-DICYCLOHEXYLETHYL)-, (2Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

PIPERIDINE, 2-(2,2-DICYCLOHEXYLETHYL)-, (Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

PEXID

Brand Name

English

2-(2,2-Dicyclohexylethyl)piperidine maleate (1:1)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C333